2023 |
Schofield LG, Kahl RGS, Rodrigues SL, Fisher JJ, Endacott SK, Delforce SJ, et al., 'Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity.', Front Cell Dev Biol, 11 1212898 (2023) [C1]
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Nova |
2022 |
Morris BJ, Katelaris A, Blumenthal NJ, Hajoona M, Sheen AC, Schrieber L, et al., 'Evidence-based circumcision policy for Australia', JOURNAL OF MENS HEALTH, 18 (2022) [C1]
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Nova |
2022 |
Tamanna S, Morosin SK, Delforce SJ, van Helden DF, Lumbers ER, Pringle KG, 'Renin-angiotensin system (RAS) enzymes and placental trophoblast syncytialisation', MOLECULAR AND CELLULAR ENDOCRINOLOGY, 547 (2022) [C1]
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Nova |
2022 |
Jarrott B, Head R, Pringle KG, Lumbers ER, Martin JH, '"LONG COVID"-A hypothesis for understanding the biological basis and pharmacological treatment strategy', PHARMACOLOGY RESEARCH & PERSPECTIVES, 10 (2022) [C1]
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Nova |
2022 |
Lumbers ER, Head R, Smith GR, Delforce SJ, Jarrott B, Martin JH, Pringle KG, 'The interacting physiology of COVID-19 and the renin-angiotensin-aldosterone system: Key agents for treatment', PHARMACOLOGY RESEARCH & PERSPECTIVES, 10 (2022) [C1]
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Nova |
2022 |
Head RJ, Lumbers ER, Jarrott B, Tretter F, Smith G, Pringle KG, et al., 'Systems analysis shows that thermodynamic physiological and pharmacological fundamentals drive COVID-19 and response to treatment', PHARMACOLOGY RESEARCH & PERSPECTIVES, 10 (2022) [C1]
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Nova |
2022 |
Barin B, Kozlakidis Z, Ricci F, Su L, Tsioutis C, Welburn SC, et al., 'Editorial: Coronavirus Disease (COVID-19): Pathophysiology, Epidemiology, Clinical Management and Public Health Response, Volume II', FRONTIERS IN PUBLIC HEALTH, 10 (2022)
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2022 |
Martin JH, Mohammed R, Delforce SJ, Skerrett-Byrne DA, de Meaultsart CC, Almazi JG, et al., 'Role of the prorenin receptor in endometrial cancer cell growth', Oncotarget, 13 587-599 (2022) [C1]
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Nova |
2021 |
Tamanna S, Clifton VL, Rae K, van Helden DF, Lumbers ER, Pringle KG, 'Angiotensin Converting Enzyme 2 (ACE2) in Pregnancy: Preeclampsia and Small for Gestational Age (vol 11, 590787, 2020)', FRONTIERS IN PHYSIOLOGY, 12 (2021)
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2021 |
Morosin SK, Delforce SJ, Corbisier de Meaultsart C, Lumbers ER, Pringle KG, 'FURIN and placental syncytialisation: a cautionary tale', CELL DEATH & DISEASE, 12 (2021) [C1]
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Nova |
2021 |
Morosin SK, Lochrin AJ, Delforce SJ, Lumbers ER, Pringle KG, 'The (pro)renin receptor ((P)RR) and soluble (pro)renin receptor (s(P)RR) in pregnancy', Placenta, 116 43-50 (2021) [C1]
The (pro)renin receptor ((P)RR) is a multi-functional protein that can be proteolytically cleaved and released in a soluble form (s(P)RR). Recently, the (P)RR and s(P)RR have beco... [more]
The (pro)renin receptor ((P)RR) is a multi-functional protein that can be proteolytically cleaved and released in a soluble form (s(P)RR). Recently, the (P)RR and s(P)RR have become of interest in pregnancy and its associated pathologies. This is because the (P)RR not only activates tissue renin angiotensin systems, but it is also an integral component of vacuolar-ATPase, activates the wingless/integrated (Wnt)/ß-catenin and extracellular signal regulated kinases 1 and 2/mitogen-activated protein kinase signalling pathways, and stabilises the ß subunit of pyruvate dehydrogenase. Additionally, s(P)RR is detected in plasma and urine, and maternal plasma levels are elevated in pregnancy complications including fetal growth restriction, preeclampsia and gestational diabetes mellitus. Therefore, s(P)RR has potential as a biomarker for these pregnancy pathologies. Preliminary functional findings suggest that s(P)RR may be important for regulating fluid balance, inflammation and blood pressure, all of which contribute to a successful pregnancy. The (P)RR and s(P)RR regulate pathways that are known to be important in maintaining pregnancy, however their role in the physiological context of pregnancy is poorly characterised. This review summarises the known and potential functions of the (P)RR and s(P)RR in pregnancy, and how their dysregulation may contribute to pregnancy complications. It also highlights the need for further research into the source and function of s(P)RR in pregnancy. Soluble (P)RR levels could be indicative of placental, kidney or liver dysfunction and therefore be a novel clinical biomarker, or therapeutic target, to improve the detection and treatment of pregnancy pathologies.
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Nova |
2021 |
Tamanna S, Lumbers ER, Morosin SK, Delforce SJ, Pringle KG, 'ACE2: A key modulator of the renin-angiotensin system and pregnancy', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 321 R833-R843 (2021) [C1]
Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound protein containing 805 amino acids. ACE2 shows approximately 42% sequence similarity to somatic ACE but has different bi... [more]
Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound protein containing 805 amino acids. ACE2 shows approximately 42% sequence similarity to somatic ACE but has different biochemical activities. The key role of ACE2 is to catalyze the vasoconstrictor peptide angiotensin (ANG) II to Ang-(1-7), thus regulating the two major counterbalancing pathways of the renin-angiotensin system (RAS). In this way, ACE2 plays a protective role in end-organ damage by protecting tissues from the proinflammatory actions of ANG II. The circulating RAS is activated in normal pregnancy and is essential for maintaining fluid and electrolyte homeostasis and blood pressure. Renin-angiotensin systems are also found in the conceptus. In this review, we summarize the current knowledge on the regulation and function of circulating and uteroplacental ACE2 in uncomplicated and complicated pregnancies, including those affected by preeclampsia and fetal growth restriction. Since ACE2 is the receptor for SARS-CoV-2, and COVID-19 in pregnancy is associated with more severe disease and increased risk of abnormal pregnancy outcomes, we also discuss the role of ACE2 in mediating some of these adverse consequences. We propose that dysregulation of ACE2 plays a critical role in the development of preeclampsia, fetal growth restriction, and COVID-19-associated pregnancy pathologies and suggest that human recombinant soluble ACE2 could be a novel therapeutic to treat and/or prevent these pregnancy complications.
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Nova |
2021 |
Morosin SK, Delforce SJ, Kahl RGS, de Meaultsart CC, Lumbers ER, Pringle KG, 'The (pro)renin receptor and soluble (pro)renin receptor in choriocarcinoma', Reproduction, 162 375-384 (2021) [C1]
This study aimed to determine if the (pro)renin receptor (ATP6AP2) changes the cellular profile of choriocarcinomas from cytotrophoblast cells to terminally syncytialised cells an... [more]
This study aimed to determine if the (pro)renin receptor (ATP6AP2) changes the cellular profile of choriocarcinomas from cytotrophoblast cells to terminally syncytialised cells and ascertain whether this impacts the invasive potential of choriocarcinoma cells. Additionally, we aimed to confirm that FURIN and/or site 1 protease (MBTPS1) cleave soluble ATP6AP2 (sATP6AP2) in BeWo choriocarcinoma cells and determine whether sATP6AP2 levels reflect the cellular profile of choriocarcinomas. BeWo choriocarcinoma cells were treated with ATP6AP2 siRNA, FURIN siRNA, DEC-RVKR-CMK (to inhibit FURIN activity), or PF 429242 (to inhibit MBTPS1 activity). Cells were also treated with forskolin, to induce syncytialisation, or vehicle and incubated for 48 h before collection of cells and supernatants. Syncytialisation was assessed by measuring hCG secretion (by ELISA) and E-cadherin protein levels (by immunoblot and immunocytochemistry). Cellular invasion was measured using the xCELLigence real-time cell analysis system and secreted sATP6AP2 levels measured by ELISA. Forskolin successfully induced syncytialisation and significantly increased both BeWo choriocarcinoma cell invasion (P < 0.0001) and sATP6AP2 levels (P= 0.02). Treatment with ATP6AP2 siRNA significantly inhibited syncytialisation (decreased hCG secretion (P= 0.005), the percent of nuclei in syncytia (P= 0.05)), forskolin-induced invasion (P= 0.046), and sATP6AP2 levels (P < 0.0001). FURIN siRNA and DEC-RVKR-CMK significantly decreased sATP6AP2 levels (both P < 0.0001). In conclusion, ATP6AP2 is important for syncytialisation of choriocarcinoma cells and thereby limits choriocarcinoma cell invasion. We postulate that sATP6AP2 could be used as a biomarker measuring the invasive potential of choriocarcinomas. Additionally, we confirmed that FURIN, not MBTPS1, cleaves sATP6AP2 in BeWo cells, but other proteases (inhibited by DEC-RVKR-CMK) may also be involved.
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Nova |
2021 |
Lee YQ, Lumbers ER, Schumacher TL, Collins CE, Rae KM, Pringle KG, 'Maternal diet influences fetal growth but not fetal kidney volume in an australian indigenous pregnancy cohort', Nutrients, 13 1-18 (2021) [C1]
Suboptimal nutrition during pregnancy is recognised as a significant modifiable determinant in the development of chronic disease in offspring in later life. The current study aim... [more]
Suboptimal nutrition during pregnancy is recognised as a significant modifiable determinant in the development of chronic disease in offspring in later life. The current study aimed: (i) to assess the dietary intakes of pregnant Indigenous Australian women against national recommendations and (ii) to investigate the associations between maternal nutrition during pregnancy and the growth of the offspring, including kidney development in late gestation in the Gomeroi gaaynggal cohort (n = 103). Maternal dietary intake in the third trimester was assessed using the Australian Eating Survey Food Frequency Questionnaire. Estimated fetal weight (EFW) and kidney size were obtained by ultrasound. Birth weight was retrieved from hospital birth records. Of the five key nutrients for optimal reproductive health (folate, iron, calcium, zinc and fibre), the nutrients with the highest percentage of pregnant women achieving the nutrient reference values (NRVs) were zinc (75.7%) and folate (57.3%), whereas iron was the lowest. Only four people achieved all NRVs (folate, iron, calcium, zinc and fibre) important in pregnancy. Sodium and saturated fat intake exceeded recommended levels and diet quality was low, with a median score of 28 out of 73 points. After adjusting for smoking and pre-pregnancy body mass index, only maternal intake of retinol equivalents and the proportion of energy from nutrient-dense or energy-dense, nutrient-poor (EDNP) foods were associated with fetal growth. EFW decreased by 0.13 g and birth weight decreased by 0.24 g for every µg increase in maternal dietary retinol intake. Interestingly, EFW, but not actual birth weight, was positively associated with percentage energy from nutrient dense foods and negatively associated with percentage energy from EDNP foods. Dietary supplement usage was associated with increased birthweight, most significantly iron and folate supplementation. Current dietary intakes of pregnant Australian women from this cohort do not align with national guidelines. Furthermore, current findings show that maternal retinol intake and diet composition during pregnancy can influence fetal growth, but not fetal kidney growth in late gestation. Strategies that aim to support and optimise nutrient intakes of Indigenous pregnant women are urgently needed. Future studies with long-term follow-up of the children in the current cohort to assess renal damage and blood pressure are imperative.
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Nova |
2020 |
Morosin SK, Delforce SJ, Lumbers ER, Pringle KG, 'Cleavage of the soluble (pro)renin receptor (sATP6AP2) in the placenta', Placenta, 101 49-56 (2020) [C1]
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Nova |
2020 |
Morosin SK, Delforce SJ, Lumbers ER, Pringle KG, 'The (pro)renin receptor (ATP6AP2) does not play a role in syncytialisation of term human primary trophoblast cells', Placenta, 97 89-94 (2020) [C1]
Introduction: In the placenta, the (pro)renin receptor (ATP6AP2) is localised to the syncytiotrophoblast. ATP6AP2 can activate the placental renin-angiotensin system (RAS), produc... [more]
Introduction: In the placenta, the (pro)renin receptor (ATP6AP2) is localised to the syncytiotrophoblast. ATP6AP2 can activate the placental renin-angiotensin system (RAS), producing Angiotensin II (Ang II) which, acting via the angiotensin II type 1 receptor (AGTR1), is important for placental development and function. ATP6AP2 can also independently stimulate intracellular signalling pathways known to regulate trophoblast syncytialisation. We proposed that ATP6AP2 plays a role in trophoblast syncytialisation. Methods: Primary trophoblast cells were isolated from human placentae and transfected with an ATP6AP2 siRNA, a negative control siRNA or vehicle and allowed to spontaneously syncytialise. Syncytialisation was determined by secretion of human chorionic gonadotrophin (hCG) and by decreased CDH1 (E-cadherin) levels. Expression of RAS mRNAs and proteins were measured by qPCR and immunoblotting, respectively. Results: Primary trophoblast cells spontaneously syncytialised in culture. Syncytialisation did not affect ATP6AP2 mRNA or protein levels. However, the expression of REN, AGT and AGTR1 mRNAs were increased (P = 0.02, P = 0.01 and P = 0.03, respectively). ATP6AP2 siRNA had no effect on syncytialisation. Discussion: In primary trophoblasts, syncytialisation was associated with increased expression of the RAS. hCG was increased during syncytialisation and is known to stimulate REN and possibly AGT, however further experiments are needed to confirm that this was the mechanism via which the RAS was activated. Therefore, syncytialisation of primary trophoblasts may involve hCG-induced RAS activation and downstream activation of signalling pathways and growth factors, which can be stimulated via the interaction of Ang II with AGTR1. Nevertheless, it appears that the (pro)renin receptor is not involved.
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Nova |
2020 |
Kandasamy Y, Rudd D, Lumbers ER, Smith R, 'An evaluation of preterm kidney size and function over the first two years of life', Pediatric Nephrology, 35 1477-1482 (2020) [C1]
Background: We carried out a study to determine the impact of prematurity on kidney development in the first 2¿years of life. Methods: In this prospective study, extremely preterm... [more]
Background: We carried out a study to determine the impact of prematurity on kidney development in the first 2¿years of life. Methods: In this prospective study, extremely preterm neonates (gestation < 28¿weeks) were recruited and underwent assessments at 6, 12, and 24¿months of age. A cohort of neonates born term were also recruited and followed up for 24¿months. The primary outcomes measured in this study were total kidney volume (TKV) and estimated glomerular filtration rate (eGFR); albuminuria and blood pressure measurements (all provided as mean (standard deviation)) were the secondary outcomes. Results: Fifty-three premature and 31 term neonates (control) were recruited. At the age of 24¿months (corrected age), infants born preterm had significantly smaller TKV (56.1 (9.4) vs. 64.8 (10.2) mL; P = 0.006). There was no difference in eGFR. These preterm infants were smaller (11.25 (1.53) vs. 12.9 (1.8) kg; P = 0.002) and shorter (83.8 (3.0) vs. 86.3 (3.4) cm; P = 0.02) when compared with the control group. At 6, 12, and 18¿months respectively, preterm infants had, relative to their height, significantly smaller kidney volumes (0.54 (0.1) vs. 0.59 (0.1) mL/cm, P = 0.05; 0.61 (0.1) vs.0.71 (0.1) mL/cm, P = 0.003; and 0.67 (0.1) vs.0.76 (0.1) mL/cm, P = 0.006). Conclusions: Relative to body length, TKV in premature infants is smaller. Since length reflects adult body proportions more accurately than BSA, TKV to height ratio may be a more important measure in the child. Despite smaller TKV (and therefore fewer nephrons), infants born prematurely achieve similar eGFRs in the first 24¿months of life, probably due to single-nephron hyperfiltration.
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Nova |
2020 |
Lumbers ER, Kandasamy Y, Delforce SJ, Boyce AC, Gibson KJ, Pringle KG, 'Programming of Renal Development and Chronic Disease in Adult Life', FRONTIERS IN PHYSIOLOGY, 11 (2020) [C1]
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Nova |
2020 |
Lumbers ER, Delforce SJ, Pringle KG, Smith GR, 'The Lung, the Heart, the Novel Coronavirus, and the Renin-Angiotensin System; The Need for Clinical Trials', FRONTIERS IN MEDICINE, 7 (2020) [C1]
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Nova |
2020 |
Tamanna S, Clifton VL, Rae K, van Helden DF, Lumbers ER, Pringle KG, 'Angiotensin Converting Enzyme 2 (ACE2) in Pregnancy: Preeclampsia and Small for Gestational Age', Frontiers in Physiology, 11 1-10 (2020) [C1]
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Nova |
2019 |
Morris BJ, Hankins CA, Lumbers ER, Mindel A, Klausner JD, Krieger JN, Cox G, 'Sex and Male Circumcision: Women's Preferences Across Different Cultures and Countries: A Systematic Review.', Sexual medicine, 7 145-161 (2019) [C1]
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Nova |
2019 |
Lumbers ER, Delforce SJ, Arthurs AL, Pringle KG, 'Causes and Consequences of the Dysregulated Maternal Renin-Angiotensin System in Preeclampsia', FRONTIERS IN ENDOCRINOLOGY, 10 (2019) [C1]
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Nova |
2019 |
Pringle KG, Lee YQ, Weatherall L, Keogh L, Diehm C, Roberts CT, et al., 'Influence of maternal adiposity, preterm birth and birth weight centiles on early childhood obesity in an Indigenous Australian pregnancy-through-to-early-childhood cohort study', Journal of Developmental Origins of Health and Disease, 10 39-47 (2019) [C1]
Childhood obesity rates are higher among Indigenous compared with non-Indigenous Australian children. It has been hypothesized that early-life influences beginning with the intrau... [more]
Childhood obesity rates are higher among Indigenous compared with non-Indigenous Australian children. It has been hypothesized that early-life influences beginning with the intrauterine environment predict the development of obesity in the offspring. The aim of this paper was to assess, in 227 mother-child dyads from the Gomeroi gaaynggal cohort, associations between prematurity, Gestation Related-Optimal Weight (GROW) centiles, maternal adiposity (percentage body fat, visceral fat area), maternal non-fasting plasma glucose levels (measured at mean gestational age of 23.1 weeks) and offspring BMI and adiposity (abdominal circumference, subscapular skinfold thickness) in early childhood (mean age 23.4 months). Maternal non-fasting plasma glucose concentrations were positively associated with infant birth weight (P=0.005) and GROW customized birth weight centiles (P=0.008). There was a significant association between maternal percentage body fat (P=0.02) and visceral fat area (P=0.00) with infant body weight in early childhood. Body mass index (BMI) in early childhood was significantly higher in offspring born preterm compared with those born at term (P=0.03). GROW customized birth weight centiles was significantly associated with body weight (P=0.01), BMI (P=0.007) and abdominal circumference (P=0.039) at early childhood. Our findings suggest that being born preterm, large for gestational age or exposed to an obesogenic intrauterine environment and higher maternal non-fasting plasma glucose concentrations are associated with increased obesity risk in early childhood. Future strategies should aim to reduce the prevalence of overweight/obesity in women of child-bearing age and emphasize the importance of optimal glycemia during pregnancy, particularly in Indigenous women.
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Nova |
2019 |
Arthurs AL, Lumbers ER, Delforce SJ, Mathe A, Morris BJ, Pringle KG, 'The role of oxygen in regulating microRNAs in control of the placental renin-angiotensin system.', Mol Hum Reprod, 25 206-217 (2019) [C1]
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Nova |
2019 |
Delforce SJ, Lumbers ER, Ellery SJ, Murthi P, Pringle K, 'Dysregulation of the placental renin-angiotensin system in human fetal growth restriction.', Reproduction (Cambridge, England), 158 237-245 (2019) [C1]
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Nova |
2019 |
Morris BJ, Hankins CA, Banerjee J, Lumbers ER, Mindel A, Klausner JD, Krieger JN, 'Does Male Circumcision Reduce Women's Risk of Sexually Transmitted Infections, Cervical Cancer, and Associated Conditions?', FRONTIERS IN PUBLIC HEALTH, 7 (2019) [C1]
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Nova |
2019 |
Delforce SJ, Lumbers ER, Morosin SK, Wang Y, Pringle KG, 'The Angiotensin II type 1 receptor mediates the effects of low oxygen on early placental angiogenesis', Placenta, 75 54-61 (2019) [C1]
Introduction: Placental development occurs in a low oxygen environment, which stimulates angiogenesis by upregulating vascular endothelial growth factor A (VEGFA), plasminogen act... [more]
Introduction: Placental development occurs in a low oxygen environment, which stimulates angiogenesis by upregulating vascular endothelial growth factor A (VEGFA), plasminogen activator inhibitor-1 (SERPINE1) and the angiopoietin-2/-1 ratio (ANGPT2/1). At this time, Angiotensin II type 1 receptor (AT1R) is highly expressed. We postulated that the early gestation placental oxygen milieu, by stimulating the angiotensin (Ang) II/AT1R pathway, increases expression of proliferative/angiogenic factors. Methods: HTR-8/SVneo cells were cultured in 1%, 5% or 20% O2 with the AT1R antagonist (losartan) for 48 h. mRNA and protein levels of angiogenic factors were determined by qPCR and ELISA. Angiogenesis and cell viability were assessed by HUVEC tube formation and resazurin assay. Results: Culture in low oxygen (1%) increased angiogenic VEGFA, SERPINE1 and placental growth factor (PGF) mRNA and VEGFA and SERPINE1 protein levels, and reduced anti-angiogenic ANGPT1, endoglin (ENG) and soluble fms-like tyrosine kinase-e15a (sFlt-e15a) mRNA (all P = 0.0001). At 1% oxygen, losartan significantly reduced intracellular VEGFA and SERPINE1 levels and secreted VEGF levels (P = 0.008, 0.0001 and 0.0001). HUVEC tube formation was increased in cells grown in HTR-8/SVneo conditioned medium from 1 to 5% cultures (all P = 0.0001). HUVECs cultured in medium from losartan treated HTR-8/SVneo cells had a reduced number of meshes, branching points and total branching length (P = 0.004, 0.003 and 0.0002). At 1% oxygen, losartan partially inhibited the oxygen-induced increase in cell viability (P = 0.0001). Discussion: Thus, AT1R blockade antagonised the low oxygen induced increase in pro-angiogenic factor expression and cell viability. Our findings highlight a role for an oxygen-sensitive Ang II/AT1R pathway during placentation.
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Nova |
2019 |
Lee YQ, Lumbers ER, Oldmeadow C, Collins CE, Johnson V, Keogh L, et al., 'The relationship between maternal adiposity during pregnancy and fetal kidney development and kidney function in infants: the Gomeroi gaaynggal study', Physiological reports, 7 1-14 (2019) [C1]
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Nova |
2019 |
Kandasamy Y, Rudd D, Lumbers ER, Smith R, 'Female preterm indigenous Australian infants have lower renal volumes than males: A predisposing factor for end-stage renal disease?', Nephrology, 24 933-937 (2019) [C1]
Aim: Indigenous Australians have an increased risk of developing chronic kidney disease (CKD). Indigenous women have a higher rate of CKD than men. In a cohort of Indigenous and n... [more]
Aim: Indigenous Australians have an increased risk of developing chronic kidney disease (CKD). Indigenous women have a higher rate of CKD than men. In a cohort of Indigenous and non-Indigenous preterm neonates, we assessed total renal volume (TRV) (a proxy indicator for nephron number). We hypothesized that there would be no difference in renal volume between these two groups at term corrected (37 weeks gestation). Methods: Normally grown preterm neonates less than 32 weeks of gestation were recruited and at term corrected dates, the neonates underwent renal ultrasonography (TRV measurements), urine microalbumin-creatinine ratio and serum analysis for Cystatin C measurement for estimated glomerular filtration rate (eGFR) calculation. Results: One hundred and five neonates (38 Indigenous; 67 non-Indigenous) were recruited. Indigenous neonates were significantly more premature and of lower birth weight. At term corrected age, Indigenous neonates had a significantly smaller TRV (18.5 (4.2) vs 21.4 (5.1) cm3; P = 0.027) despite no significant difference in body weight. Despite having a smaller TRV, there was no significant difference in eGFR between Indigenous and Non-indigenous neonates (47.8 [43.2¿50.4] vs 46.2 [42.6¿53.3] ml/min per 1.73 m2; P = 0.986). These infants achieve similar eGFR through hyperfiltration, which likely increases their future risk of CKD. There was no difference in microalbumin-creatinine ratio. Female Indigenous neonates, however, had significantly smaller TRV compared with Indigenous male neonates (15.9 (3.6) vs 20.6 (3.6) cm3; P = 0.006), despite no difference in eGFR, birth weight, gestational age, and weight at term corrected. Conclusion: The difference in TRV is likely to be an important risk factor for the difference in morbidity and mortality from renal disease reported between male and female Indigenous adults.
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Nova |
2019 |
Arthurs AL, Lumbers ER, Pringle KG, 'MicroRNA mimics that target the placental renin-angiotensin system inhibit trophoblast proliferation.', Mol Hum Reprod, 25 218-227 (2019) [C1]
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Nova |
2019 |
Mah BL, Pringle KG, Weatherall L, Keogh L, Schumacher T, Eades S, et al., 'Pregnancy stress, healthy pregnancy and birth outcomes - The need for early preventative approaches in pregnant Australian Indigenous women: A prospective longitudinal cohort study', Journal of Developmental Origins of Health and Disease, 10 31-38 (2019) [C1]
Adverse pregnancy outcomes including prematurity and low birth weight (LBW) have been associated with life-long chronic disease risk for the infant. Stress during pregnancy increa... [more]
Adverse pregnancy outcomes including prematurity and low birth weight (LBW) have been associated with life-long chronic disease risk for the infant. Stress during pregnancy increases the risk of adverse pregnancy outcomes. Many studies have reported the incidence of adverse pregnancy outcomes in Indigenous populations and a smaller number of studies have measured rates of stress and depression in these populations. This study sought to examine the potential association between stress during pregnancy and the rate of adverse pregnancy outcomes in Australian Indigenous women residing in rural and remote communities in New South Wales. This study found a higher rate of post-traumatic stress disorder, depression and anxiety symptoms during pregnancy than the general population. There was also a higher incidence of prematurity and LBW deliveries. Unfortunately, missing post-traumatic stress disorder and depressive symptomatology data impeded the examination of associations of interest. This was largely due to the highly sensitive nature of the issues under investigation, and the need to ensure adequate levels of trust between Indigenous women and research staff before disclosure and recording of sensitive research data. We were unable to demonstrate a significant association between the level of stress and the incidence of adverse pregnancy outcomes at this stage. We recommend this longitudinal study continue until complete data sets are available. Future research in this area should ensure prioritization of building trust in participants and overestimating sample size to ensure no undue pressure is placed upon an already stressed participant.
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Nova |
2018 |
Diehm CJ, Lumbers ER, Weatherall L, Keogh L, Eades S, Brown A, et al., 'Assessment of Fetal Kidney Growth and Birth Weight in an Indigenous Australian Cohort', FRONTIERS IN PHYSIOLOGY, 8 (2018) [C1]
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Nova |
2018 |
Wang Y, Lumbers ER, Arthurs AL, de Meaultsart CC, Mathe A, Avery-Kiejda KA, et al., 'Regulation of the human placental (pro)renin receptor-prorenin-angiotensin system by microRNAs.', Molecular human reproduction, 24 453-464 (2018) [C1]
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Nova |
2018 |
Eiby YA, Shrimpton NY, Wright IMR, Lumbers ER, Colditz PB, Duncombe GJ, Lingwood BE, 'Reduced blood volume decreases cerebral blood flow in preterm piglets', Journal of Physiology, 596 6033-6041 (2018) [C1]
Key points: Preterm infants often have poor cardiovascular function that is associated with adverse neurodevelopmental outcomes. Preterm infants may be vulnerable to hypovolaemia ... [more]
Key points: Preterm infants often have poor cardiovascular function that is associated with adverse neurodevelopmental outcomes. Preterm infants may be vulnerable to hypovolaemia due to excessive vasodilatation and leaky capillaries. Following reduction in blood volume, cardiac output and mean arterial pressure were reduced to the same extent in term and preterm piglets. Cerebral blood flow was maintained following blood volume reduction in term but not in preterm piglets. Effective detection and treatment of functional hypovolaemia may reduce the risk of brain injury in preterm infants. Abstract: Preterm infants often have impaired cardiovascular function that may contribute to poor neurodevelopmental outcomes. The study aimed to determine the effects of reduced blood volume on cardiovascular function, including cerebral blood flow, in preterm and term piglets. In preterm (97/115¿days) and term piglets, up to 10% of the estimated blood volume was removed. Removal of blood was stopped if MAP dropped below 20¿mmHg. Heart rate, cardiac contractility and relaxation, cardiac output, mean arterial pressure (MAP), and cerebral blood flow were measured at baseline and again after blood volume reduction. The volume of blood removed was less in preterm piglets than in term piglets (5.1¿±¿1.8¿vs. 7.7¿±¿0.9¿mL¿kg-1, mean¿±¿SD, P¿<¿0.001). Cardiac output and MAP decreased to the same extent in term and preterm piglets. Cerebral blood flow decreased in preterm but not term piglets and cerebral vascular conductance increased in term piglets only. Compensatory responses to maintain cerebral blood flow after blood volume reduction are active in term piglets but not in preterm piglets. As a result, even a small reduction in blood volume, or an increase in the capacity of the circulatory system leading to functional hypovolaemia, may lead to a significant reduction in cerebral blood flow and contribute to brain injury in preterm neonates.
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Nova |
2018 |
Kandasamy Y, Rudd D, Smith R, Lumbers ER, Wright IM, 'Extra uterine development of preterm kidneys.', Pediatric nephrology (Berlin, Germany), 33 1007-1012 (2018) [C1]
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Nova |
2018 |
Pringle KG, de Meaultsart CC, Sykes SD, Weatherall LJ, Keogh L, Clausen DC, et al., 'Urinary angiotensinogen excretion in Australian Indigenous and non-Indigenous pregnant women', Pregnancy Hypertension, 12 110-117 (2018) [C1]
The intrarenal renin-angiotensin system (iRAS) is implicated in the pathogenesis of hypertension, chronic kidney disease and diabetic nephropathy. Urinary angiotensinogen (uAGT) l... [more]
The intrarenal renin-angiotensin system (iRAS) is implicated in the pathogenesis of hypertension, chronic kidney disease and diabetic nephropathy. Urinary angiotensinogen (uAGT) levels reflect the activity of the iRAS and are altered in women with preeclampsia. Since Indigenous Australians suffer high rates and early onset of renal disease, we hypothesised that Indigenous Australian pregnant women, like non-Indigenous women with pregnancy complications, would have altered uAGT levels. The excretion of RAS proteins was measured in non-Indigenous and Indigenous Australian women with uncomplicated or complicated pregnancies (preeclampsia, diabetes/gestational diabetes, proteinuria/albuminuria, hypertension, small/large for gestational age, preterm birth), and in non-pregnant non-Indigenous women. Non-Indigenous pregnant women with uncomplicated pregnancies, had higher uAGT/creatinine levels than non-Indigenous non-pregnant women (P < 0.01), and levels increased as pregnancy progressed (P < 0.001). In non-Indigenous pregnant women with pregnancy complications, uAGT/creatinine was suppressed in the third trimester (P < 0.01). In Indigenous pregnant women with uncomplicated pregnancies, there was no change in uAGT/creatinine with gestational age and uAGT/creatinine was lower in the 2nd and 3rd trimesters than in non-Indigenous pregnant women with uncomplicated pregnancies (P < 0.03, P < 0.007, respectively). The uAGT/creatinine ratios of Indigenous women with uncomplicated or complicated pregnancies were the same. A decrease in uAGT/creatinine with advancing gestational age was associated with increased urinary albumin/creatinine, as is seen in preeclampsia, but it was not specific for this disorder. The reduced uAGT/creatinine in Indigenous pregnant women may reflect subclinical renal dysfunction which limits the ability of the kidney to maintain sodium balance and could indicate an increased risk of pregnancy complications and/or future renal disease.
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Nova |
2017 |
Pringle KG, Zakar T, Lumbers ER, 'The intrauterine renin angiotensin system: Sex-specific effects on the prevalence of spontaneous preterm birth', Clinical and Experimental Pharmacology and Physiology, 44 605-610 (2017) [C1]
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Nova |
2017 |
Delforce SJ, Lumbers ER, Pringle KG, 'Regulation of the prorenin - angiotensin system by oxygen and miRNAs; parallels between placentation and tumour development?', Placenta, 56 27-33 (2017) [C1]
Tissue renin-angiotensin systems (RASs) are involved in tissue growth and development as they are important regulators of angiogenesis, cell proliferation and migration. The place... [more]
Tissue renin-angiotensin systems (RASs) are involved in tissue growth and development as they are important regulators of angiogenesis, cell proliferation and migration. The placental RAS is most highly expressed in early gestation, at a time when the oxygen tension within the conceptus is reduced, and plays a key role in placental growth and development. Similar to the placenta, tumour development relies on proliferation, angiogenesis and invasion in order to grow and metastasize. The RAS is known to be upregulated in a variety of solid tumours, including ovarian, endometrial, cervical, breast and prostate. This review explores the roles of oxygen and microRNAs in regulating the normal expression of the placental RAS, providing insight into regulation of its development as well as the development of disease states in which the RAS is overexpressed. We propose that the placental RAS is downregulated by microRNAs that are suppressed during the physiologically normal ¿hypoxic¿ phase of early placentation. Suppression of these miRNAs allows the placental RAS to stimulate placental growth and angiogenesis. We propose that similar mechanisms may be at play in solid tumours, which are characterised by hypoxia.
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Nova |
2017 |
Delforce SJ, Lumbers ER, de Meaultsart CC, Wang Y, Proietto A, Otton G, et al., 'Expression of renin-angiotensin system (RAS) components in endometrial cancer', ENDOCRINE CONNECTIONS, 6 9-19 (2017) [C1]
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Nova |
2017 |
Mah B, Weatherall L, Burrows J, Blackwell CC, Gwynn J, Wadhwa P, et al., 'Post-traumatic stress disorder symptoms in pregnant Australian Indigenous women residing in rural and remote New South Wales: A cross-sectional descriptive study', Australian and New Zealand Journal of Obstetrics and Gynaecology, 57 520-525 (2017) [C1]
Background: Pregnancy can be a stressful time for many women. There is ample evidence of numerous physical and mental health inequities for Indigenous Australians. For those Indig... [more]
Background: Pregnancy can be a stressful time for many women. There is ample evidence of numerous physical and mental health inequities for Indigenous Australians. For those Indigenous women who are pregnant, it is established that there is a higher incidence of poor physical perinatal outcomes when compared with non-Indigenous Australians. However, little evidence exists that examines stressful events and post-traumatic stress disorder (PTSD) symptoms in pregnant women who are members of this community. Aims: To quantify the rates of stressful events and PTSD symptoms in pregnant Indigenous women. Methods: One hundred and fifty rural and remote Indigenous women were invited to complete a survey during each trimester of their pregnancy. The survey measures were the stressful life events and the Impact of Events Scale. Results: Extremely high rates of PTSD symptoms were reported by participants. Approximately 40% of this group exhibited PTSD symptoms during their pregnancy with mean score 33.38 (SD¿=¿14.37) significantly higher than a study of European victims of crisis, including terrorism attacks (20.6, SD¿=¿18.5). Conclusions: The extreme levels of PTSD symptoms found in the women participating in this study are likely to result in negative implications for both mother and infant. An urgent response must be mounted at government, health, community development and research levels to address these findings. Immediate attention needs to focus on the development of interventions to address the¿high¿levels of PTSD symptoms that pregnant Australian Indigenous women¿experience.
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Nova |
2016 |
Eiby YA, Shrimpton NY, Wright IMR, Lumbers ER, Colditz PB, Duncombe GJ, Lingwood BE, 'Inotropes do not increase cardiac output or cerebral blood flow in preterm piglets', Pediatric Research, 80 870-879 (2016) [C1]
Background:The preterm newborn is at high risk of developing cardiovascular compromise during the first day of life and this is associated with increased risk of brain injury. Sta... [more]
Background:The preterm newborn is at high risk of developing cardiovascular compromise during the first day of life and this is associated with increased risk of brain injury. Standard treatments are volume expansion and administration of inotropes, typically dopamine and/or dobutamine, but there is limited evidence that inotropes improve clinical outcomes. This study investigated the efficacy of dopamine and dobutamine for the treatment of cardiovascular compromise in the preterm newborn using a piglet model.Methods:Preterm and term piglets were assigned to either dopamine, dobutamine or control infusions. Heart rate, left ventricular contractility, cardiac output, blood pressure, and cerebral and regional blood flows were measured during baseline, low (10 µg/kg/h), and high (20 µg/kg/h) dose infusions.Results:At baseline, preterm piglets had lower cardiac contractility, cardiac output, blood pressure, and cerebral blood flow compared to term piglets. The response of preterm piglets to either dopamine or dobutamine administration was less than in term piglets. In both preterm and term piglets, cardiac output and cerebral blood flow were unaltered by either inotrope.Conclusion:In order to provide better cardiovascular support, it may be necessary to develop treatments that target receptors with a more mature profile than adrenoceptors in the preterm newborn.
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Nova |
2016 |
Ashman AM, Collins CE, Weatherall L, Brown LJ, Rollo ME, Clausen D, et al., 'A cohort of Indigenous Australian women and their children through pregnancy and beyond: The Gomeroi gaaynggal study', Journal of Developmental Origins of Health and Disease, 7 357-368 (2016) [C1]
Indigenous Australians have high rates of chronic diseases, the causes of which are complex and include social and environmental determinants. Early experiences in utero may also ... [more]
Indigenous Australians have high rates of chronic diseases, the causes of which are complex and include social and environmental determinants. Early experiences in utero may also predispose to later-life disease development. The Gomeroi gaaynggal study was established to explore intrauterine origins of renal disease, diabetes and growth in order to inform the development of health programmes for Indigenous Australian women and children. Pregnant women are recruited from antenatal clinics in Tamworth, Newcastle and Walgett, New South Wales, Australia, by Indigenous research assistants. Measures are collected at three time points in pregnancy and from women and their children at up to eight time points in the child's first 5 years. Measures of fetal renal development and function include ultrasound and biochemical biomarkers. Dietary intake, infant feeding and anthropometric measurements are collected. Standardized procedures and validated tools are used where available. Since 2010 the study has recruited over 230 women, and retained 66 postpartum. Recruitment is ongoing, and Gomeroi gaaynggal is currently the largest Indigenous pregnancy-through-early-childhood cohort internationally. Baseline median gestational age was 39.1 weeks (31.5-43.2, n=110), median birth weight was 3180 g (910-5430 g, n=110). Over one third (39.3%) of infants were admitted to special care or neonatal nursery. Nearly half of mothers (47.5%) reported tobacco smoking during pregnancy. Results of the study will contribute to knowledge about origins of chronic disease in Indigenous Australians and nutrition and growth of women and their offspring during pregnancy and postpartum. Study strengths include employment and capacity-building of Indigenous staff and the complementary ArtsHealth programme.
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Nova |
2016 |
Grimson S, Cox AJ, Pringle KG, Burns C, Lumbers ER, Blackwell CC, Scott RJ, 'The prevalence of unique SNPs in the renin-angiotensin system highlights the need for pharmacogenetics in Indigenous Australians', Clinical and Experimental Pharmacology and Physiology, 43 157-160 (2016) [C1]
Genetic differences between ethnic populations affect susceptibility to disease and efficacy of drugs. This study examined and compared the prevalence of single nucleotide polymor... [more]
Genetic differences between ethnic populations affect susceptibility to disease and efficacy of drugs. This study examined and compared the prevalence of single nucleotide polymorphisms (SNPs) in genes of the renin-angiotensin system (RAS) in a desert community of Indigenous Australians and in non-Indigenous Australians. The polymorphisms were angiotensinogen, AGT G-217A (rs5049); AGT G+174A (rs4762); Angiotensin II type 1 receptor, AGTR1 A+1166C (rs5186); angiotensin converting enzyme, ACE A-240T (rs4291), ACE T-93C (rs4292); renin, REN T+1142C (rs5706). They were measured using allelic discrimination assays. The prevalence of REN T+1142C SNP was similar in the two populations; 99% were homozygous for the T allele. All other SNPs were differently distributed between the two populations (P < 0.0001). In non-Indigenous Australians, the A allele at position 204 of ACE rs4291 was prevalent (61.8%) whereas in the Indigenous Australians the A allele was less prevalent (28%). For rs4292, the C allele had a prevalence of 37.9% in non-Indigenous Australians but in Indigenous Australians the prevalence was only 1%. No Indigenous individuals were homozygous for the C allele of AGTR1 (rs5186). Thus the prevalence of RAS SNPs in this Indigenous Australian desert community was different from non-Indigenous Australians as was the prevalence of cytokine SNPs (as shown in a previous study). These differences may affect susceptibility to chronic renal and cardiovascular disease and may alter the efficacy of drugs used to inhibit the RAS. These studies highlight the need to study the pharmacogenetics of drug absorption, distribution, metabolism and excretion in Indigenous Australians for safe prescribing guidelines.
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Nova |
2016 |
Delforce SJ, Wang Y, Van-Aalst ME, Corbisier De Meaultsart C, Morris BJ, Broughton-Pipkin F, et al., 'Effect of oxygen on the expression of renin-angiotensin system components in a human trophoblast cell line', Placenta, 37 1-6 (2016) [C1]
During the first trimester, normal placental development occurs in a low oxygen environment that is known to stimulate angiogenesis via upregulation of vascular endothelial growth... [more]
During the first trimester, normal placental development occurs in a low oxygen environment that is known to stimulate angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Expression of the placental renin-angiotensin system (RAS) is highest in early pregnancy. While the RAS and oxygen both stimulate angiogenesis, how they interact within the placenta is unknown. We postulated that low oxygen increases expression of the proangiogenic RAS pathway and that this is associated with increased VEGF in a first trimester human trophoblast cell line (HTR-8/SVneo). HTR-8/SVneo cells were cultured in one of three oxygen tensions (1%, 5% and 20%). RAS and VEGF mRNA expression were determined by qPCR. Prorenin, angiotensin converting enzyme (ACE) and VEGF protein levels in the supernatant, as well as prorenin and ACE in cell lysates, were measured using ELISAs. Low oxygen significantly increased the expression of both angiotensin II type 1 receptor (AGTR1) and VEGF (both P < 0.05). There was a positive correlation between AGTR1 and VEGF expression at low oxygen (r = 0.64, P < 0.005). Corresponding increases in VEGF protein were observed with low oxygen (P < 0.05). Despite no change in ACE1 mRNA expression, ACE levels in the supernatant increased with low oxygen (1% and 5%, P < 0.05). Expression of other RAS components did not change. Low oxygen increased AGTR1 and VEGF expression, as well as ACE and VEGF protein levels, suggesting that the proangiogenic RAS pathway is activated. This highlights a potential role for the placental RAS in mediating the proangiogenic effects of low oxygen in placental development.
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Nova |
2016 |
Pringle KG, Delforce SJ, Wang Y, Ashton KA, Proietto A, Otton G, et al., 'Renin-angiotensin system gene polymorphisms and endometrial cancer', ENDOCRINE CONNECTIONS, 5 128-135 (2016) [C1]
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Nova |
2015 |
Wang Y, Lumbers ER, Sykes SD, Pringle KG, 'Regulation of the renin-angiotensin system pathways in the human decidua', Reproductive Sciences, 22 865-872 (2015) [C1]
Pregnancy outcome is influenced, in part, by the sex of the fetus. Decidual renin messenger RNA (REN) abundance is greater in women carrying a female fetus than a male fetus. Here... [more]
Pregnancy outcome is influenced, in part, by the sex of the fetus. Decidual renin messenger RNA (REN) abundance is greater in women carrying a female fetus than a male fetus. Here, we explore whether the sex of the fetus also influences the regulation of decidual RAS expression with a known stimulator of renal renin and cyclic adenosine monophosphate (cAMP). Cyclic adenosine monophosphate had no affect on decidual REN expression, since REN abundance was still greater in decidual explants from women carrying a female fetus than a male fetus after cAMP treatment. Cyclic adenosine monophosphate decreased prorenin levels in the supernatant if the fetus was female (ie, prorenin levels were no longer sexually dimorphic) and altered the fetal sex-specific differences in other RAS genes seen in vitro. Therefore, fetal sex influences the decidual renin-angiotensin system response to cAMP. This may be related to the presence of fetal cells in the maternal decidua.
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Nova |
2015 |
Pringle KG, Conquest A, Mitchell C, Zakar T, Lumbers ER, 'Effects of Fetal Sex on Expression of the (Pro)renin Receptor and Genes Influenced by its Interaction With Prorenin in Human Amnion', Reproductive Sciences, 22 750-757 (2015) [C1]
Males are more likely to be born preterm than females. The causes are unknown, but it is suggested that intrauterine tissues regulate fetal growth and survival in a sex-specific m... [more]
Males are more likely to be born preterm than females. The causes are unknown, but it is suggested that intrauterine tissues regulate fetal growth and survival in a sex-specific manner. We postulated that prorenin binding to its prorenin/renin receptor receptor (ATP6AP2) would act in a fetal sex-specific manner in human amnion to regulate the expression of promyelocytic zinc finger, a negative regulator of ATP6AP2 expression as well as 2 pathways that might influence the onset of labor, namely transforming growth factor ß1 (TGFB1) and prostaglandin endoperoxide synthase 2 (PTGS2). Our findings demonstrate that there are strong interactions between prorenin, ATP6AP2, and TGFB1 and that this system has a greater capacity in female amnion to stimulate profibrotic pathways, thus maintaining the integrity of the fetal membranes. In contrast, glucocorticoids or other factors independent of the prorenin/prorenin receptor pathway may be important regulators of PTGS2 in human pregnancy.
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Nova |
2015 |
Standen P, Sferruzzi-Perri AN, Taylor R, Heinemann G, Zhang JV, Highet AR, et al., 'Maternal insulin-like growth factor 1 and 2 differentially affect the renin-angiotensin system during pregnancy in the guinea pig', GROWTH HORMONE & IGF RESEARCH, 25 141-147 (2015) [C1]
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Nova |
2015 |
Pringle KG, Wang Y, Lumbers ER, 'The synthesis, secretion and uptake of prorenin in human amnion.', Physiological reports, 3 e12313 (2015) [C1]
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Nova |
2015 |
White AJR, Cheruvu SC, Sarris M, Liyanage SS, Lumbers E, Chui J, et al., 'Expression of classical components of the renin-angiotensin system in the human eye', JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM, 16 59-66 (2015) [C1]
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2015 |
Sykes SD, Mitchell C, Pringle KG, Wang Y, Zakar T, Lumbers ER, 'Methylation of promoter regions of genes of the human intrauterine renin angiotensin system and their expression', International Journal of Endocrinology, 2015 (2015) [C1]
The intrauterine renin angiotensin system (RAS) is implicated in placentation and labour onset. Here we investigate whether promoter methylation of RAS genes changes with gestatio... [more]
The intrauterine renin angiotensin system (RAS) is implicated in placentation and labour onset. Here we investigate whether promoter methylation of RAS genes changes with gestation or labour and if it affects gene expression. Early gestation amnion and placenta were studied, as were term amnion, decidua, and placenta collected before labour (at elective caesarean section) or after spontaneous labour and delivery. The expression and degree of methylation of the prorenin receptor (ATP6AP2), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), and two proteases that can activate prorenin (kallikrein, KLK1, and cathepsin D, CTSD) were measured by qPCR and a DNA methylation array. There was no effect of gestation or labour on the methylation of RAS genes and CTSD. Amnion and decidua displayed strong correlations between the percent hypermethylation of RAS genes and CTSD, suggestive of global methylation. There were no correlations between the degree of methylation and mRNA abundance of any genes studied. KLK1 was the most methylated gene and the proportion of hypermethylated KLK1 alleles was lower in placenta than decidua. The presence of intermediate methylated alleles of KLK1 in early gestation placenta and in amnion after labour suggests that KLK1 methylation is uniquely dynamic in these tissues.
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Nova |
2015 |
Pringle KG, Weatherall L, Corbisier de Meaultsart C, Keogh L, Sands S, Blackwell C, et al., 'The Gomeroi Gaaynggal Cohort: A Preliminary Study of the Maternal Determinants of Pregnancy Outcomes in Indigenous Australian Women', Journal of Pregnancy and Child Health, 3 (2015) [C1]
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Nova |
2015 |
Pringle KG, Rae K, Weatherall L, Hall S, Burns C, Smith R, et al., 'Effects of maternal inflammation and exposure to cigarette smoke on birth weight and delivery of preterm babies in a cohort of Indigenous Australian women', Frontiers in Immunology, 6 (2015) [C1]
Sudden infant death syndrome (SIDS), neonatal deaths, and deaths from infection are higher among Indigenous Australians. This study aimed to determine the effects of inflammatory ... [more]
Sudden infant death syndrome (SIDS), neonatal deaths, and deaths from infection are higher among Indigenous Australians. This study aimed to determine the effects of inflammatory responses and exposure to cigarette smoke, two important factors associated with sudden death in infancy, on preterm birth, and birth weight in a cohort of Indigenous mothers. Indigenous Australian women (n = 131) were recruited as part of a longitudinal study while attending antenatal care clinics during pregnancy; blood samples were collected up to three times in pregnancy. Serum cotinine, indicating exposure to cigarette smoke, was detected in 50.4% of mothers. Compared with non-Indigenous women, the cohort had 10 times the prevalence of antibodies to Helicobacter pylori (33 vs. 3%). Levels of immunoglobulin G, antibodies to H. pylori, and C-reactive protein (CRP) were all inversely correlated with gestational age (P < 0.05). CRP levels were positively associated with maternal body mass index (BMI; ¿ = 0.449, P = 0.001). The effects of cigarette smoke (cotinine) and inflammation (CRP) were assessed in relation to risk factors for SIDS: gestational age at delivery and birth weight. Serum cotinine levels were negatively associated with birth weight (¿ = -0.37, P < 0.001), this correlation held true for both male (¿ = -0.39, P = 0.002) and female (¿ = -0.30, P = 0.017) infants. Cotinine was negatively associated with gestational age at delivery (¿ = -0.199, P = 0.023). When assessed by fetal sex, this was significant only for males (¿ = -0.327, P = 0.011). CRP was negatively associated with gestational age at delivery for female infants (¿ = -0.46, P < 0.001). In contrast, maternal BMI was significantly correlated with birth weight. These data highlight the importance of putting programs in place to reduce cigarette smoke exposure in pregnancy and to treat women with chronic infections such as H. pylori to improve pregnancy outcomes and decrease risk factors for sudden death in infancy.
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Nova |
2015 |
Lumbers ER, Wang Y, Delforce SJ, Corbisier de Meaultsart C, Logan PC, Mitchell MD, Pringle KG, 'Decidualisation of human endometrial stromal cells is associated with increased expression and secretion of prorenin', Reproductive Biology and Endocrinology, 13 (2015) [C1]
Background: In pregnancy, the decidualised endometrium expresses high levels of prorenin and other genes of the renin-angiotensin system (RAS) pathway. In this study we aimed to d... [more]
Background: In pregnancy, the decidualised endometrium expresses high levels of prorenin and other genes of the renin-angiotensin system (RAS) pathway. In this study we aimed to determined if the RAS was present in endometrial stromal cells and if decidualisation upregulated the expression of prorenin, the prorenin receptor ((P)RR) and associated RAS pathways. Immortalised human endometrial stromal cells (HESCs) can be stimulated to decidualise by combined treatment with medroxyprogesterone acetate (MPA), 17ß-estradiol (E2) and cAMP (MPA-mix) or with 5-aza-2'-deoxycytidine (AZA), a global demethylating agent. Methods: HESCs were incubated for 10days with one of the following treatments: vehicle, MPA-mix, a combination of medroxyprogesterone acetate (MPA) and estradiol-17ß alone, or AZA. Messenger RNA abundance and protein levels of prorenin (REN), the (P)RR (ATP6AP2), angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), vascular endothelial growth factor (VEGF), and plasminogen activator inhibitor-1 (PAI-1) were measured by real-time PCR and ELISA's, respectively. Promyelocytic zinc finger (PLZF) and phospho-inositol-3 kinase (PIK3R1) mRNA abundances were also measured. Results: HESCs expressed the prorenin receptor (ATP6AP2), REN, AGT, ACE and low levels of AGTR1. MPA-mix and AZA stimulated expression of REN. Prorenin protein secretion was increased in MPA-mix treated HESCs. E2 + MPA had no effect on any RAS genes. MPA-mix treatment was associated with increased VEGF (VEGFA) and PAI-1 (SERPINE1) mRNA and VEGF protein. Conclusions: An endometrial prorenin receptor/renin angiotensin system is activated by decidualisation. Since (P)RR is abundant, the increase in prorenin secretion could have stimulated VEGF A and SERPINE1 expression via Ang II, as both ACE and AGTR1 are present, or by Ang II independent pathways. Activation of the RAS in human endometrium with decidualisation, through stimulation of VEGF expression and secretion, could be critical in establishing an adequate blood supply to the developing maternal placental vascular bed.
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Nova |
2015 |
Kim E, Lingwood B, Eiby Y, Lumbers E, Boyce A, Gibson K, 'Expression of genes of the cardiac and renal renin angiotensin systems in preterm piglets: Is this system a suitable target for therapeutic intervention?', Therapeutic Advances in Cardiovascular Disease, 9 285-296 (2015) [C1]
The newborn circulating, cardiac and renal renin¿angiotensin systems (RASs) are essential for blood pressure control, and for cardiac and renal development. If cardiac and renal R... [more]
The newborn circulating, cardiac and renal renin¿angiotensin systems (RASs) are essential for blood pressure control, and for cardiac and renal development. If cardiac and renal RASs are immature this may contribute to cardiovascular compromise in preterm infants. This study measured mRNA expression of cardiac and renal RAS components in preterm, glucocorticoid (GC) exposed preterm, and term piglets. Methods: Renal and cardiac RAS mRNA levels were measured using real-time polymerase chain reaction (PCR). Genes studied were: (pro)renin receptor, renin, angiotensinogen, angiotensin converting enzyme (ACE), ACE2, angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R). Results: All the genes studied were expressed in the kidney; neither renin nor AT2R mRNA were detected in the heart. There were no gestational changes in (pro)renin receptor, renin, ACE or AT1R mRNA levels. Right ventricular angiotensinogen mRNA levels in females were lower in preterm animals than at term, and GC exposure increased levels in male piglets. Renal angiotensinogen mRNA levels in female term piglets were lower than females from both preterm groups, and lower than male term piglets. Left ventricular ACE2 mRNA expression was lower in GC treated preterm piglets. Renal AT2R mRNA abundance was highest in GC treated preterm piglets, and the AT1R/AT2R ratio was increased at term. Preterm cardiac and renal RAS mRNA levels were similar to term piglets, suggesting that immaturity of these RASs does not contribute to preterm cardiovascular compromise. Since preterm expression of both renal and cardiac angiotensin II-AT1R is similar to term animals, cardiovascular dysfunction in the sick preterm human neonate might be effectively treated by agents acting on their RASs. © 2015, SAGE Publications. All rights reserved.
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Nova |
2015 |
Pringle KG, Sykes SD, Lumbers ER, 'Circulating and intrarenal renin-angiotensin systems in healthy men and nonpregnant women.', Physiol Rep, 3 (2015) [C1]
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Nova |
2014 |
Sykes SD, Pringle KG, Zhou A, Dekker GA, Roberts CT, Lumbers ER, SCOPE Consortium, 'The balance between human maternal plasma angiotensin II and angiotensin 1-7 levels in early gestation pregnancy is influenced by fetal sex.', J Renin Angiotensin Aldosterone Syst, 15 523-531 (2014) [C1]
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Nova |
2014 |
Kandasamy Y, Smith R, Lumbers ER, Rudd D, 'Nephrin - a biomarker of early glomerular injury.', Biomarker Research, 2 1-8 (2014) [C1]
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Nova |
2014 |
Kim MY, Eiby YA, Lumbers ER, Wright LL, Gibson KJ, Barnett AC, Lingwood BE, 'Effects of glucocorticoid exposure on growth and structural maturation of the heart of the preterm piglet', PLoS ONE, 9 (2014) [C1]
Inadequate maintenance of systemic blood flow in neonates following preterm birth is associated with increased morbidity and mortality, and may be due in part to structural immatu... [more]
Inadequate maintenance of systemic blood flow in neonates following preterm birth is associated with increased morbidity and mortality, and may be due in part to structural immaturity of the myocardium. Maternal glucocorticoid administration is associated with improved cardiovascular function, and possibly promotes structural maturation of the myocardium. This study assessed the structural maturity of the myocardium in male and female preterm and term piglets, and preterm piglets exposed to a regimen of maternal glucocorticoids as used clinically. In preterm, term and glucocorticoid exposed preterm piglets cardiomyocyte maturity was examined by measuring the proportion of binucleated myocytes and the volumes of single living ventricular cardiomyocytes with fluorescence microscopy. Ventricular apoptosis and proliferation were measured by immunohistochemistry. Preterm piglet hearts had fewer binucleated myocytes, smaller myocytes, and more proliferative and fewer apoptotic nuclei than term hearts. Maternal glucocorticoid treatment resulted in increased binucleation with no increase in myocyte volume, and levels of proliferation and apoptosis that were more similar to the term heart. Atrial weights were increased and in female piglets there was an increase in the ratio of left to right ventricular weight. The observed changes in atrial mass and myocyte structural maturation correlated with changes in cardiac function of isolated hearts of littermates. In conclusion, the association between increased myocardial maturation following glucocorticoid exposure, improved cardiac function in littermates, and clinical improvement in human neonatal cardiac function exposed to antenatal glucocorticoids, suggests that glucocorticoid exposure contributes to improved cardiovascular function in preterm infants by promoting myocardial structural maturity. © 2014 Kim et al.
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Nova |
2014 |
Kim MY, Finch AM, Lumbers ER, Boyce AC, Gibson KJ, Eiby YA, Lingwood BE, 'Expression of adrenoceptor subtypes in preterm piglet heart is different to term heart', PLoS ONE, 9 (2014) [C1]
Preterm delivery increases the risk of inadequate systemic blood flow and hypotension, and many preterm infants fail to respond to conventional inotrope treatments. If the profile... [more]
Preterm delivery increases the risk of inadequate systemic blood flow and hypotension, and many preterm infants fail to respond to conventional inotrope treatments. If the profile of cardiac adrenoceptor subtypes in the preterm neonate is different to that at term this may contribute to these clinical problems. This study measured mRNA expression of ß1, ß2, a1A, a2A and a2B-adrenoceptor subtypes by real time PCR in term (113d), preterm (91d) and preterm piglets (91d) exposed to maternal glucocorticoid treatment. Abundance of ß-adrenoceptor binding sites in the left ventricle was measured using saturation binding assays. Relative abundance of ß1-adrenoceptor mRNA in untreated preterm hearts was ~50% of term abundance in both left and right ventricles (P>0.001). Trends in receptor binding site density measurements supported this observation (P = 0.07). Glucocorticoid exposure increased ß1-adrenoceptor mRNA levels in the right ventricle of preterm hearts (P = 0.008) but did not alter expression in the left ventricle (P>0.1). Relative abundance of a1A-adrenoceptor mRNA was the same in preterm and term piglet hearts (P = >0.1) but was reduced by maternal glucocorticoid treatment (P<0.01); a2A-adrenoceptor mRNA abundance was higher in untreated and glucocorticoid exposed preterm piglet hearts than in term piglets (P<0.001). There was no difference between male and female piglets in mRNA abundance of any of the genes studied. In conclusion, there is reduced mRNA abundance of ß1-adrenoceptors in the preterm pig heart. If this lower expression of ß-adrenoceptors occurs in human preterm infants, it could explain their poor cardiovascular function and their frequent failure to respond to commonly used inotropes. © 2014 Kim et al.
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Nova |
2014 |
Eiby YA, Lumbers ER, Staunton MP, Wright LL, Colditz PB, Wright IM, Lingwood BE, 'Endogenous angiotensins and catecholamines do not reduce skin blood flow or prevent hypotension in preterm piglets.', Physiological reports, 2 1-13 (2014) [C1]
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Nova |
2014 |
Lumbers ER, Pringle KG, 'Roles of the circulating renin-angiotensin-aldosterone system in human pregnancy', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 306 R91-R101 (2014) [C1]
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Nova |
2014 |
Sykes SD, Pringle KG, Zhou A, Dekker GA, Roberts CT, Lumbers ER, 'Fetal sex and the circulating renin-angiotensin system during early gestation in women who later develop preeclampsia or gestational hypertension', Journal of Human Hypertension, 28 133-139 (2014) [C1]
There are fetal sex-specific differences in the balance between angiotensin (Ang) II and Ang-(1-7) in the maternal circulation during pregnancy. To determine whether at 15 weeks&a... [more]
There are fetal sex-specific differences in the balance between angiotensin (Ang) II and Ang-(1-7) in the maternal circulation during pregnancy. To determine whether at 15 weeks' gestation plasma levels of Ang II and Ang-(1-7), as well as levels of prorenin and Ang-converting enzyme (ACE), predicted the development of gestational hypertension (GH) or preeclampsia (PreE) and were associated with estimates of fetal and maternal health, women who later developed GH (n=50) or PreE (n=50) were compared with body mass index-matched controls (n=100). Women who subsequently developed PreE or GH had increased Ang-(1-7) levels at 15 weeks' gestation compared with women with normal pregnancies. When separated by fetal sex, this difference was seen only in women carrying a female fetus. Prorenin and ACE concentrations were not useful biomarkers for the prediction of either PreE or GH at 15 weeks' gestation. Women with a male fetus who developed PreE and women who subsequently developed GH had increased blood pressures at 15 weeks' gestation compared with women with normal pregnancies, suggesting that these women were on an early trajectory for the development of hypertension. We propose that measurement of Ang-(1-7) during early gestation could be useful in predicting, those women who will go on to develop new-onset hypertension in pregnancy.
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Nova |
2014 |
Rae KM, Weatherall L, Blackwell CC, Pringle K, Smith R, Lumbers E, 'Long conversations: Gomeroi gaaynggal tackles renal disease in the Indigenous community', Australasian Epidemiologist, 21 44-48 (2014) [C2]
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Nova |
2014 |
Kandasamy Y, Smith R, Wright IMR, Lumbers ER, 'Reduced nephron endowment in the neonates of Indigenous Australian peoples', JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, 5 31-35 (2014) [C1]
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Nova |
2013 |
Zhou A, Dekker GA, Lumbers ER, Lee SY, Thompson SD, McCowan LME, Roberts CT, 'The association of
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Nova |
2013 |
Wang Y, Pringle KG, Lumbers ER, 'The effects of cyclic AMP, sex steroids and global hypomethylation on the expression of genes controlling the activity of the renin-angiotensin system in placental cell lines', PLACENTA, 34 275-280 (2013) [C1]
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Nova |
2013 |
Kandasamy Y, Smith R, Wright IMR, Lumbers ER, 'Extra-uterine renal growth in preterm infants: Oligonephropathy and prematurity', PEDIATRIC NEPHROLOGY, 28 1791-1796 (2013) [C1]
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2013 |
Mitchell CM, Sykes SD, Pan X, Pringle KG, Lumbers ER, Hirst JJ, Zakar T, 'Inflammatory and steroid receptor gene methylation in the human amnion and decidua', JOURNAL OF MOLECULAR ENDOCRINOLOGY, 50 267-277 (2013) [C1]
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Nova |
2013 |
Kandasamy Y, Smith R, Wright IMR, Lumbers ER, 'Relationships between glomerular filtration rate and kidney volume in low-birth-weight neonates', JOURNAL OF NEPHROLOGY, 26 894-898 [C1]
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Nova |
2013 |
Zhou A, Dekker GA, Lumbers ER, Leemaqz SY, Thompson SD, Heinemann G, et al., 'The association of maternal
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Nova |
2013 |
Morrison JL, Lumbers E, Bennet L, Black J, 'Frontiers in Research Review: ISH Early Origins of Hypertension Workshop: Early Life Exposure and Development of a Healthy Heart Introduction: Celebrating Emeritus Scientia Professor Eugenie R Lumbers AM and Professor Caroline McMillen', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 40 740-742 (2013) [C3]
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2013 |
Lumbers ER, Pringle KG, Wang Y, Gibson KJ, 'The renin-angiotensin system from conception to old age: the good, the bad and the ugly', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 40 743-752 (2013) [C1]
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Nova |
2013 |
Rae K, Weatherall L, Hollebone K, Apen K, McLean M, Blackwell C, et al., 'Developing research in partnership with Aboriginal communities - strategies for improving recruitment and retention', RURAL AND REMOTE HEALTH, 13 (2013) [C2]
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Nova |
2013 |
Eiby YA, Wright LL, Kalanjati VP, Miller SM, Bjorkman ST, Keates HL, et al., 'A Pig Model of the Preterm Neonate: Anthropometric and Physiological Characteristics', PLOS ONE, 8 (2013) [C1]
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Nova |
2013 |
Morrison JL, Lumbers E, Ozanne SE, Suter CM, 'The Australian Early Origins of Hypertension workshop: a celebration of the scientific contributions made by emeritus Scientia professor Eugenie R lumbers AM and professor Caroline McMillen', JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, 4 325-327 (2013) [C3]
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Nova |
2012 |
Wang Y, Pringle KG, Sykes SD, Marques FZ, Morris BJ, Zakar T, Lumbers ER, 'Fetal sex affects expression of renin-angiotensin system components in term human decidua', Endocrinology, 153 462-468 (2012) [C1]
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Nova |
2012 |
Wang Y, Pringle KG, Chen Y, Zakar T, Lumbers ER, 'Regulation of the renin-angiotensin system (RAS) in BeWo and HTR-8/SVneo trophoblast cell lines', Placenta, 33 634-639 (2012) [C1]
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Nova |
2012 |
Eiby YA, Lumbers ER, Headrick JP, Lingwood BE, 'Left ventricular output and aortic blood flow in response to changes in preload and afterload in the preterm piglet heart', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 303 (2012) [C1]
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2011 |
Pringle KG, Zakar T, Roach DM, Mitchell CM, Hirst JJ, Lumbers ER, 'Molecular evidence of a (pro)renin/(pro)renin receptor system in human intrauterine tissues in pregnancy and its association with PGHS-2', Journal of the Renin-Angiotensin-Aldosterone System, 12 304-310 (2011) [C1]
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Nova |
2011 |
Marques FZ, Pringle KG, Conquest AL, Hirst JJ, Markus MA, Sarris M, et al., 'Molecular characterization of renin-angiotensin system components in human intrauterine tissues and fetal membranes from vaginal delivery and cesarean section', Placenta, 32 214-221 (2011) [C1]
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Nova |
2011 |
Brandon AE, Boyce AC, Lumbers ER, Kumarasamy V, Gibson KJ, 'Programming of the renin response to haemorrhage by mild maternal renal impairment in sheep', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 38 102-108 (2011) [C1]
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2011 |
van der Graaf AM, Zeeman GG, Groen H, Lumbers ER, Roberts C, Dekker GA, 'O15. Non-invasive assessment of hemodynamics in early pregnancy.', Pregnancy hypertension, 1 264 (2011)
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2011 |
Pringle KG, Tadros MA, Callister RJ, Lumbers ER, 'The expression and localization of the human placental prorenin/renin-angiotensin system throughout pregnancy: Roles in trophoblast invasion and angiogenesis?', Placenta, 32 956-962 (2011) [C1]
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2009 |
Lumbers ER, Kim MY, Burrell JH, Kumarasamy V, Boyce AC, Gibson KJ, et al., 'Effects of intrafetal IGF-I on growth of cardiac myocytes in late-gestation fetal sheep', AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 296 E513-E519 (2009) [C1]
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2009 |
Brandon AE, Boyce AC, Lumbers ER, Gibson KJ, 'Maternal renal dysfunction in sheep is associated with salt insensitivity in female offspring', JOURNAL OF PHYSIOLOGY-LONDON, 587 261-270 (2009) [C1]
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2008 |
Brandon AE, Boyce AC, Lumbers ER, Zimanyj MA, Bertram JF, Gibson KJ, 'Glomerular hypertrophy in offspring of subtotally nephrectomized ewes', ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, 291 318-324 (2008) [C1]
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2008 |
Boyce AC, Gibson KJ, Thomson CL, Lumbers ER, 'Interactions between maternal subtotal nephrectomy and salt: effects on renal function and the composition of plasma in the late gestation sheep fetus', EXPERIMENTAL PHYSIOLOGY, 93 262-270 (2008) [C1]
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2008 |
Gibson KJ, Boyce AC, Thomson CL, Chinchen S, Lumbers ER, 'Interactions between subtotal nephrectomy and salt: Effects on blood pressure and renal function in pregnant and nonpregnant ewes', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 294 (2008) [C1]
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Nova |
2007 |
Roberts CT, Standen P, Sferruzzi-Perri AN, Owens JA, Kumarasamy V, Lumbers ER, 'Novel but distinct interactions of insulin-like growth factors (IGFs) with the placental renin-angiotensin system in early gestation in guinea pigs', EARLY HUMAN DEVELOPMENT, 83 S146-S146 (2007)
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2007 |
Gibson KJ, Boyce AC, Karime BM, Lumbers ER, 'Maternal renal insufficiency alters plasma composition and renal function in the fetal sheep', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 292 R1204-R1211 (2007)
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Nova |
2007 |
Yu Z-Y, McKay K, van Asperen P, Zheng M, Fleming J, Ginn SL, et al., 'Lentivirus vector-mediated gene transfer to the developing bronchiolar airway epithelium in the fetal lamb', JOURNAL OF GENE MEDICINE, 9 429-439 (2007)
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2007 |
Boyce AC, Gibson KJ, Wintour EM, Koukoulas I, Gatford KL, Owens JA, Lumbers ER, 'The kidney is resistant to chronic hypoglycaemia in late-gestation fetal sheep', CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 85 597-605 (2007)
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2006 |
Matuszek MA, Gibson KJ, Lumbers ER, Simonetta G, 'Impact of cortisol on alpha-actin content in vascular smooth muscle cells of fetal sheep', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 33 197-203 (2006)
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Nova |
2006 |
Gibson KJ, Thomson CL, Boyce AC, Karime BM, Lumbers ER, 'Effects of a reduction in maternal renal mass on pregnancy and cardiovascular and renal function of the pregnant ewe', AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 290 F1153-F1162 (2006)
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Nova |
2005 |
Campbell DJ, Johnston CI, Kelly DJ, Lumbers ER, Menard J, Ryan JW, Wilkinson-Berka JL, 'Sandford Lloyd Skinner (1933-2005) - In memoriam', HYPERTENSION, 46 452-453 (2005)
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2005 |
Lumbers ER, Boyce AC, Joulianos G, Kumarasamy V, Barner E, Segar JL, Burrell JH, 'Effects of cortisol on cardiac myocytes and on expression of cardiac genes in fetal sheep', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 288 R567-R574 (2005)
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Nova |
2005 |
Boyce AC, Gibson KJ, Wintour EM, Koukoulas I, Lumbers ER, 'Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 289 R1099-R1106 (2005)
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Nova |
2003 |
Burrell JH, Boyn AM, Kumarasamy V, Hsieh A, Head SI, Lumbers ER, 'Growth and maturation of cardiac myocytes in fetal sheep in the second half of gestation', ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY, 274A 952-961 (2003)
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2003 |
O'Connell AE, Boyce AC, Lumbers ER, Gibson KJ, 'The effects of asphyxia on renal function in fetal sheep at midgestation', JOURNAL OF PHYSIOLOGY-LONDON, 552 933-943 (2003)
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Nova |
2003 |
Lumbers ER, Yu ZY, Crawford EN, 'Effects of fetal behavioral states on renal sympathetic nerve activity and arterial pressure of unanesthetized fetal sheep', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 285 R908-R916 (2003)
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2003 |
Lumbers ER, Yu Z-Y, Crawford EN, 'Effects of fetal behavioral states on renal sympathetic nerve activity and arterial pressure of unanesthetized fetal sheep.', American journal of physiology. Regulatory, integrative and comparative physiology, 285 R908-R916 (2003)
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2002 |
Marsh AC, Lumbers ER, Gibson KJ, 'Renal, cardiovascular and endocrine responses of fetal sheep at 0.8 of gestation to an infusion of amino acids.', The Journal of physiology, 540 717-728 (2002)
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2002 |
McMullen JR, Gibson KJ, Lumbers ER, Burrell JH, '125I[Sar(1)Ile(8)] angiotensin II has a different affinity for AT(1) and AT(2) receptor subtypes in ovine tissues.', Regulatory peptides, 105 83-92 (2002)
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Nova |
2002 |
Marsh AC, Lumbers ER, Gibson KJ, 'Renal, cardiovascular and endocrine responses of fetal sheep at 0.8 of gestation to an infusion of amino acids', JOURNAL OF PHYSIOLOGY-LONDON, 540 717-728 (2002)
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2002 |
McMullen JR, Gibson KJ, Lumbers ER, Burrell JH, 'I-125[Sar(1)Ile(8)] Angiotensin II has a different affinity for AT(1) and AT(2) receptor subtypes in ovine tissues', REGULATORY PEPTIDES, 105 83-92 (2002)
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2002 |
Yu ZY, Lumbers ER, Simonetta G, 'The cardiovascular and renal effects of acute and chronic inhibition of nitric oxide production in fetal sheep', EXPERIMENTAL PHYSIOLOGY, 87 343-351 (2002)
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Nova |
2002 |
Yu ZY, Lumbers ER, 'Effects of birth on baroreceptor-mediated changes in heart rate variability in lambs and fetal sheep', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 29 455-463 (2002)
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Nova |
2002 |
Lumbers ER, 'Exercise in pregnancy: Physiological basis of exercise prescription for the pregnant woman', JOURNAL OF SCIENCE AND MEDICINE IN SPORT, 5 20-31 (2002)
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2001 |
Marsh AC, Gibson KJ, Wu J, Owens PC, Owens JA, Lumbers ER, 'Insulin-like growth factor I alters renal function and stimulates renin secretion in late gestation fetal sheep', JOURNAL OF PHYSIOLOGY-LONDON, 530 253-262 (2001)
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2001 |
Marsh AC, Gibson KJ, Wu J, Owens PC, Owens JA, Lumbers ER, 'Insulin-like growth factor I alters renal function and stimulates renin secretion in late gestation fetal sheep', Journal of Physiology, 530 253-262 (2001)
1. While it is known that treatment with insulin-like growth factor I (IGF-I) stimulates growth of the fetal kidney, nothing is known about the short term or long term effects of ... [more]
1. While it is known that treatment with insulin-like growth factor I (IGF-I) stimulates growth of the fetal kidney, nothing is known about the short term or long term effects of IGF-I on fetal renal function. To investigate the acute effects of IGF-I on fetal renal function and on the activity of the fetal renin-angiotensin system, studies were carried out in 12 chronically catheterized fetal sheep aged 120 ± 1 days, before and during a 4 h I.V. infusion of IGF-I at 80 µg h-1. Seven control fetuses were infused over the same period with vehicle (0.1% bovine serum albumin in 0.15 M saline). 2. IGF-I infusion increased plasma IGF-I concentrations by about 80%. There was a small fall in arterial PO2 (P < 0.01), arterial PCO2 increased (P < 0.05), plasma lactate levels increased (P < 0.01) and arterial pH fell (P < 0.05). Fractional bicarbonate reabsorption increased and bicarbonate excretion decreased (P < 0.05). 3. Infusions of IGF-I had no sustained effect on fetal arterial pressure. Glomerular filtration rate (GFR) did not change significantly during IGF-I infusion, but renal blood flow (RBF) fell (P < 0.05). Therefore filtration fraction relative to control values increased (P < 0.05), suggesting that efferent arteriolar vasoconstriction had occurred. 4. IGF-I infusion led to an antidiuresis (P < 0.01), a rise in urinary osmolality (P < 0.05) and a fall in free water clearance (P < 0.01). Since fetal PO2 fell, it is probable that these effects were mediated by arginine vasopressin. 5. The excretion rates of sodium, chloride and phosphate were all reduced by 4 h of infusion (P < 0.05), because their fractional reabsorption rates were all increased (sodium, P < 0.01; chloride, P < 0.01; and phosphate, P < 0.05). 6. Plasma renin concentration increased by 275 ± 52% during infusion of IGF-I (P < 0.005). Plasma renin activity also increased (P < 0.005), while circulating angiotensinogen concentrations fell (P < 0.05). 7. In the adult, IGF-I increases both RBF and GFR, enhances tubular reabsorption and stimulates the renin-angiotensin system. In the fetus, however, it decreased RBF and had no effect on GFR, but was associated with enhanced tubular function and intense stimulation of renin secretion. Some of these effects of IGF-I on fetal renal function may be involved in maturation of the kidney in preparation for life after birth.
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Nova |
2001 |
McMullen JR, Gibson KJ, Lumbers ER, Burrell JH, 'Selective down-regulation of AT(2) receptors in uterine arteries from pregnant ewes given 24-h intravenous infusions of angiotensin II', REGULATORY PEPTIDES, 99 119-129 (2001)
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2001 |
Lumbers ER, Gunn AJ, Zhang DY, Wu JJ, Maxwell L, Bennet L, 'Nonimmune hydrops fetalis and activation of the renin-angiotensin system after asphyxia in preterm fetal sheep', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 280 R1045-R1051 (2001)
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Nova |
2001 |
Burrell JH, Hegarty BD, McMullen JR, Lumbers ER, 'Effects of gestation on ovine fetal and maternal angiotensin receptor subtypes in the heart and major blood vessels', EXPERIMENTAL PHYSIOLOGY, 86 71-82 (2001)
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2001 |
Lumbers ER, Yu ZY, Gibson KJ, 'The selfish brain and the Barker hypothesis', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 28 942-947 (2001)
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Nova |
2001 |
Marsh AC, Gibson KJ, Wu J, Owens PC, Owens JA, Lumbers ER, 'Chronic effect of insulin-like growth factor I on renin synthesis, secretion, and renal function in fetal sheep', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 281 R318-R326 (2001)
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Nova |
2001 |
Marsh AC, Gibson KJ, Wu J, Owens PC, Owens JA, Lumbers ER, 'Chronic effect of insulin-like growth factor I on renin synthesis, secretion, and renal function in fetal sheep', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 281 (2001)
In the adult, insulin-like growth factor I (IGF-I) increases glomerular filtration rate (GFR) and renal blood flow (RBF) during both acute and chronic treatment. To study its effe... [more]
In the adult, insulin-like growth factor I (IGF-I) increases glomerular filtration rate (GFR) and renal blood flow (RBF) during both acute and chronic treatment. To study its effects on the developing kidney, chronically catheterized fetal sheep (120 ± 1 days gestation) were infused intravenously for up to 10 days with 80 µg/h IGF-I (n = 5) or vehicle (0.1% BSA in saline, n = 6). In contrast to previous acute studies in adult rats and humans, after 4 h of IGF-I fetal GFR and RBF were unchanged. Fractional sodium reabsorption increased (P < 0.05). However, by 4 days, GFR per kilogram had risen by 35 ± 13% (P < 0.05), whereas RBF remained unchanged. Tubular growth and maturation may have occurred, as proximal tubular sodium reabsorption increased by ~35% (P < 0.005). Therefore, despite a marked increase in filtered sodium (~30%, P < 0.05), fractional sodium reabsorption did not change. Although the effects of IGF-I on renal function were delayed, plasma renin activity and concentration were both elevated after 4 h and remained high at 4 days (P < 0.05). Despite this, arterial pressure and heart rate did not change. Kidneys of IGF-Iinfused fetuses weighed ~30% more (P = 0.05) and contained ~75% more renin than control fetuses (P < 0.005). Thus, in the fetus, the renal effects of long-term IGF-I infusion are very different from the adult, possibly because IGF-I stimulated kidney growth.
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2001 |
Lumbers ER, Gunn AJ, Zhang DY, Wu JJ, Maxwell L, Bennet L, 'Nonimmune hydrops fetalis and activation of the renin-angiotensin system after asphyxia in preterm fetal sheep.', American journal of physiology. Regulatory, integrative and comparative physiology, 280 R1045-R1051 (2001)
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2000 |
Zhang DY, Lumbers ER, Simonetta G, Wu JJ, Owens JA, Robinson JS, McMillen IC, 'Effects of placental insufficiency on the ovine fetal renin-angiotensin system', EXPERIMENTAL PHYSIOLOGY, 85 79-84 (2000) [C1]
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2000 |
Zhang DY, Lumbers ER, Simonetta G, Wu JJ, Owens JA, McMillen IC, 'Effects of placental insufficiency on the ovine fetal renin-angiotensin system', Experimental Physiology, 85 79-84 (2000)
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2000 |
Hegarty BD, Burrell JH, Gibson KJ, McMullen JR, Lumbers ER, 'Effect of cortisol on fetal ovine vascular angiotensin II receptors and contractility', EUROPEAN JOURNAL OF PHARMACOLOGY, 406 439-448 (2000)
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2000 |
Yu ZY, Lumbers ER, 'Measurement of baroreceptor-mediated effects on heart rate variability in fetal sheep', PEDIATRIC RESEARCH, 47 233-239 (2000)
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Nova |
2000 |
Gibson KJ, McMullen JR, Lumbers ER, 'Renal acid-base and sodium handling in hypoxia and subsequent mild metabolic acidosis in foetal sheep', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 27 67-73
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2000 |
Yu ZY, Lumbers ER, 'Effect of cold on fetal heart rate and its variability', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 27 607-611 (2000)
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Nova |
2000 |
Lumbers ER, 'Fetal renal circulation', Advances in Organ Biology, 9 275-299 (2000)
This chapter details the development of the renal vasculature, the RAS, and the neural supply to the kidney. The sensitivity of the developing kidney to disruption of the activity... [more]
This chapter details the development of the renal vasculature, the RAS, and the neural supply to the kidney. The sensitivity of the developing kidney to disruption of the activity of the fetal RAS is described. The fetal kidney has a high RVR and a low RBF and GFR. The effects on RBF and GFR of the RSNs, vasoactive peptides, and endothelium-derived factors such as NO are described. There are several unique features about the fetal renal vascular responses. First, it appears that endothelin can mediate a vasodilator response in the fetal circulation through stimulation of NO production. Second, stimulation of RSNs after adrenoreceptor blockade causes renal vasodilation. © 2000.
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1999 |
McMullen JR, Gibson KJ, Lumbers ER, Burrell JH, Wu J, 'Interactions between AT(1) and AT(2) receptors in uterine arteries from pregnant ewes', EUROPEAN JOURNAL OF PHARMACOLOGY, 378 195-202 (1999)
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Nova |
1999 |
Lumbers ER, Yu ZY, 'A method for determining baroreflex-mediated sympathetic and parasympathetic control of the heart in pregnant and non-pregnant sheep', JOURNAL OF PHYSIOLOGY-LONDON, 515 555-566 (1999)
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1999 |
Dodic M, Peers A, Coghlan JP, May CN, Lumbers E, Yu ZY, Wintour EM, 'Altered cardiovascular haemodynamics and baroreceptor-heart rate reflex in adult sheep after prenatal exposure to dexamethasone', CLINICAL SCIENCE, 97 103-109 (1999)
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Nova |
1999 |
Burrell JH, Lumbers ER, Bernasconi C, 'Effects of ACTH-induced hypertension in the pregnant ewe', JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 34 818-823 (1999)
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1999 |
Stevens AD, Lumbers ER, 'The effects of long-term infusions of angiotensin II into the pregnant ewe on uterine blood flow and on the fetus', JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 34 824-830 (1999)
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1999 |
Lumbers ER, 'Angiotensin and aldosterone', REGULATORY PEPTIDES, 80 91-100 (1999)
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1999 |
Gibson KJ, Lumbers ER, 'Effects of bilateral nephrectomy and angiotensin II replacement on body fluids in foetal sheep', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 26 765-773 (1999)
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1998 |
Lumbers ER, Bernasconi C, Burrell JH, 'Effects of infusions of ACTH in the chronically catheterized pregnant ewe and her fetus', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 274 (1998)
To study the effects of elevated maternal levels of adrenocorticotropic hormone (ACTH) on the fetus, nine chronically catheterized pregnant ewes (132 ± 0.9 days of gestation) were... [more]
To study the effects of elevated maternal levels of adrenocorticotropic hormone (ACTH) on the fetus, nine chronically catheterized pregnant ewes (132 ± 0.9 days of gestation) were infused intravenously for 3 days with Synacthen (5 µg · kg-1 · day-1). Four ewes were given 0.15 M saline intravenously over the same period. ACTH induced hypertension in the ewe. Mean arterial pressure (MAP) increased from 101 ± 4.4 to 114 ± 3.9 mmHg at 48 h (P < 0.05); cardiac output increased from 8.6 ± 0.5 to 10.4 ± 1.0 1/min after 24 h (P < 0.05). Within 2-4 h, maternal cortisol levels increased from 24.6 ± 6.3 to 287 ± 30 nM (P < 0.05) and remained high. Fetal plasma cortisol levels increased from 20 ± 4.5 to 60 ± 4.5 nM (P < 0.05) within 2- 4 h and then increased further. Fetal MAP was increased at 24 h. There was no effect on fetal blood gases or pH. Ewes became hyperglycemic and lactacidemic by 24 h (P < 0.05), and the fetuses were also hyperglycemic and lactacidemic (P < 0.05) at this time. There were no changes in fetuses carried by saline- infused ewes. Both ewes and fetuses had raised plasma osmolalities and, since hematocrit fell, retained fluid. Ewes became hypokalemic; the fetuses did not, but there was an increase in fetal K excretion. Thus ACTH-induced hypertension in the ewe had minimal effects on fetal MAP, fetal blood gas status, and pH. The fetus, however, did show many of the other effects of maternal glucocorticoid and mineralocorticoid excess, partly because its cortisol levels were increased but also as a consequence of metabolic and endocrine changes in the ewe.
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1998 |
McMullen JR, Gibson KJ, Lumbers ER, 'Effects of intravenous infusions of noradrenaline on renal function in chronically catheterised fetal sheep', BIOLOGY OF THE NEONATE, 73 254-263 (1998)
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1998 |
Segar JL, Lumbers ER, Nuyt AM, SMith OJ, Robillard JE, 'Effect of antenatal glucocorticoids on sympathetic nerve activity at birth in preterm sheep', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 274 R160-R167 (1998)
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Nova |
1998 |
Lumbers ER, Bernasconi C, Burrell JH, 'Effects of infusions of ACTH in the chronically catheterized pregnant ewe and her fetus', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 274 R445-R452 (1998)
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Nova |
1998 |
Zhang DY, Lumbers ER, Wu JJ, 'Gestational changes in fetal renal and hepatic angiotensinogen mRNA and protein', REPRODUCTION FERTILITY AND DEVELOPMENT, 10 399-404 (1998)
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1998 |
Yu ZY, Lumbers ER, Gibson KJ, Stevens AD, 'Effects of hypoxaemia on foetal heart rate, variability and cardiac rhythm', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 25 577-584
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1997 |
Gibson KJ, Lumbers ER, 'Ovine fetal cardiovascular, renal, and fluid balance responses to 3 days of high arginine vasopressin levels', American Journal of Physiology, 272 (1997)
-To determine the effects of sustained high levels of arginine vasopressin (AVP) on the fetus and whether these effects were the same as those found during acute infusion of AVP, ... [more]
-To determine the effects of sustained high levels of arginine vasopressin (AVP) on the fetus and whether these effects were the same as those found during acute infusion of AVP, chronically catheterized fetal sheep aged 121-136 days were infused for 3 days with either AVP (45 mU·kg-1- h-1) or saline. The bradycardia, acidemia, and failure of glomerulotubular balance that occurred with acute AVP infusion were reversed by day 3 of AVP (P < 0.005) and the acute rise in arterial pressure was attenuated (P < 0.005). By contrast, the rise in the glomerular filtration rate was sustained (P < 0.005) and urinary osmolality increased further to 426 ± 30 mosmol/kg (P < 0.01). Although placental blood flow did not change acutely with AVP, it had fallen by day 3 (P < 0.01). In addition, with AVP but not saline extracellular volume fell from 588 ±28 to 493 ±29 ml/kg (P < 0.002) and the plasma/interstitial volume ratio rose from 0.18 ±0.01 to 0.21 ±0.01 (P = 0.001). These findings suggest that although release of AVP may be beneficial in acute stress in utero, sustained high levels may be detrimental to fetal health and sodium balance. 1 Copyright ö1997 the American Physiological Society.
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1997 |
Burrell JH, Lumbers ER, 'Angiotensin receptor subtypes in the uterine artery during ovine pregnancy', EUROPEAN JOURNAL OF PHARMACOLOGY, 330 257-267 (1997)
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Nova |
1997 |
Lumbers ER, Burrell JH, Stevens AD, Weir BA, 'Effects of one-clip, one-kidney hypertension in chronically catheterized pregnant ewes', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 24 336-343 (1997)
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Nova |
1997 |
Lumbers ER, 'Effects of drugs on uteroplacental blood flow and the health of the foetus', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 24 864-868 (1997)
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Nova |
1997 |
Gibson KJ, Lumbers ER, 'Ovine fetal cardiovascular, renal, and fluid balance responses to 3 days of high arginine vasopressin levels', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 272 R1069-R1076 (1997)
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1997 |
Gibson KJ, Lumbers ER, 'Ovine fetal cardiovascular, renal, and fluid balance responses to 3 days of high arginine vasopressin levels', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 272 (1997)
To determine the effects of sustained high levels of arginine vasopressin (AVP) on the fetus and whether these effects were the same as those found during acute infusion of AVP, c... [more]
To determine the effects of sustained high levels of arginine vasopressin (AVP) on the fetus and whether these effects were the same as those found during acute infusion of AVP, chronically catheterized fetal sheep aged 121-136 days were infused for 3 days with either AVP (45 mU · kg-1 · h-1) or saline. The bradycardia, acidemia, and failure of glomerulotubular balance that occurred with acute AVP infusion were reversed by day 3 of AVP (P < 0.005) and the acute rise in arterial pressure was attenuated (P < 0.005). By contrast, the rise in the glomerular filtration rate was sustained (P < 0.005) and urinary osmolality increased further to 426 ± 30 mosmol/kg (P < 0.01). Although placental blood flow did not change acutely with AVP, it had fallen by day 3 (P < 0.01). In addition, with AVP but not saline extracellular volume fell from 588 ± 28 to 493 ± 29 ml/kg (P < 0.002) and the plasma/interstitial volume ratio rose from 0.18 ± 0.01 to 0.21 ± 0.01 (P = 0.001). These findings suggest that although release of AVP may be beneficial in acute stress in utero, sustained high levels may be detrimental to fetal health and sodium balance.
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1997 |
Gibson KJ, Lumbers ER, 'Ovine fetal cardiovascular, renal, and fluid balance responses to 3 days of high arginine vasopressin levels', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 272 (1997)
To determine the effects of sustained high levels of arginine vasopressin (AVP) on the fetus and whether these effects were the same as those found during acute infusion of AVP, c... [more]
To determine the effects of sustained high levels of arginine vasopressin (AVP) on the fetus and whether these effects were the same as those found during acute infusion of AVP, chronically catheterized fetal sheep aged 121-136 days were infused for 3 days with either AVP (45 mU · kg-1 · h-1) or saline. The bradycardia, acidemia, and failure of glomerulotubular balance that occurred with acute AVP infusion were reversed by day 3 of AVP (P < 0.005) and the acute rise in arterial pressure was attenuated (P < 0.005). By contrast, the rise in the glomerular filtration rate was sustained (P < 0.005) and urinary osmolality increased further to 426 ± 30 mosmol/kg (P < 0.01). Although placental blood flow did not change acutely with AVP, it had fallen by day 3 (P < 0.01). In addition, with AVP but not saline extracellular volume fell from 588 ± 28 to 493 ± 29 ml/kg (P < 0.002) and the plasma/interstitial volume ratio rose from 0.18 ± 0.01 to 0.21 ± 0.01 (P = 0.001). These findings suggest that although release of AVP may be beneficial in acute stress in utero, sustained high levels may be detrimental to fetal health and sodium balance.
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1996 |
Zhang DYL, Lumbers ER, Simonetta G, 'Changes in renal renin gene expression in fetal sheep', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 23 682-684 (1996)
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1996 |
Lumbers ER, Burrell JH, Stevens AD, Bernasconi C, 'Responses of fetal sheep to reduced maternal renal blood flow and maternal hypertension', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 271 (1996)
In 16 chronically catheterized fetal sheep the effects of reducing and restoring maternal renal blood flow (RBF) and thus inducing and reversing hypertension were studied in unine... [more]
In 16 chronically catheterized fetal sheep the effects of reducing and restoring maternal renal blood flow (RBF) and thus inducing and reversing hypertension were studied in uninephrectomized pregnant ewes; controls were 3 fetuses that were carried by uninephrectomized ewes in which RBF was not reduced and that did not become hypertensive. Within 24-72 h of maternal RBF reduction, fetal arterial PO2 had fallen (P < 0.001) and PCO2 had increased (P < 0.025); fetal arterial pressure also increased (P < 0.005). These effects persisted, despite restoration of maternal RBF and reversal of maternal hypertension. Within 24-72 h of reduction of maternal RBF, fetal urine flow had increased (P < 0.005), and it remained elevated over the first 3 h after RBF was restored; 24-72 h later it was lower (P < 0.025) and returned to control levels. The excretion of sodium, potassium, and chloride showed a similar increase when maternal RBF was reduced (P < 0.001), with return to control values 24-72 h after RBF had been restored. Fetal glomerular filtration rate did not change; thus the natriuresis and diuresis that occurred were due to reduced tubular solute and water reabsorption (P < 0.025). These changes in fetal renal function may be related, in part, to changes in fetal PO2 and PCO2, but they are most likely due to reduced maternal renal function due to the restriction in maternal RBF, inasmuch as they were reversed when RBF was restored.
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1996 |
Lumbers ER, Bernasconi C, Burrell JH, 'Effects of inhibition of the maternal renin-angiotensin system on maternal and fetal responses to drainage of fetal fluids', CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 74 973-982 (1996)
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Nova |
1996 |
Gibson KJ, Lumbers ER, 'The effects of continuous drainage of fetal fluids on salt and water balance in fetal sheep', JOURNAL OF PHYSIOLOGY-LONDON, 494 443-450 (1996)
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1996 |
Lumbers ER, Burrell JH, Stevens AD, Bernasconi C, 'Responses of fetal sheep to reduced maternal renal blood flow and maternal hypertension', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 271 R1691-R1700 (1996)
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1996 |
Stevenson KM, Gibson KJ, Lumbers ER, 'Effects of losartan on the cardiovascular system, renal haemodynamics and function and lung liquid flow in fetal sheep', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 23 125-133 (1996)
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1995 |
STEVENSON KM, GIBSON KJ, LUMBERS ER, 'COMPARISON OF THE TRANSPLACENTAL TRANSFER OF ENALAPRIL, CAPTOPRIL AND LOSARTAN IN SHEEP', BRITISH JOURNAL OF PHARMACOLOGY, 114 1495-1501 (1995)
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1995 |
STEVENS AD, LUMBERS ER, 'EFFECTS OF INTRAVENOUS INFUSIONS OF NORADRENALINE INTO THE PREGNANT EWE ON UTERINE BLOOD-FLOW, FETAL RENAL-FUNCTION, AND LUNG LIQUID FLOW', CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 73 202-208 (1995)
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1995 |
GIBSON KJ, LUMBERS ER, 'EXTRACELLULAR VOLUME AND BLOOD-VOLUME IN CHRONICALLY CATHETERIZED FETAL SHEEP', JOURNAL OF PHYSIOLOGY-LONDON, 485 835-844 (1995)
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1995 |
STEVENSON KM, LUMBERS ER, 'EFFECTS OF ANGIOTENSIN-II IN FETAL SHEEP AND MODIFICATION OF ITS ACTIONS BY INDOMETHACIN', JOURNAL OF PHYSIOLOGY-LONDON, 487 147-158 (1995)
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1995 |
LUMBERS ER, 'DEVELOPMENT OF RENAL-FUNCTION IN THE FETUS - A REVIEW', REPRODUCTION FERTILITY AND DEVELOPMENT, 7 415-426 (1995)
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1995 |
Lumbers ER, Moore RS, Stevens AD, 'Effects of changes in colloid osmotic pressure on excretion of sodium by the ovine fetal kidney', REPRODUCTION FERTILITY AND DEVELOPMENT, 7 1321-1327 (1995)
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1995 |
LUMBERS ER, 'FUNCTIONS OF THE RENIN-ANGIOTENSIN SYSTEM DURING DEVELOPMENT', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 22 499-505 (1995)
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1994 |
NAIL BS, LUMBERS ER, STEVENS AD, 'THE EFFECT OF FETAL LUNG-INFLATION ON FETAL HEART-RATE', AMERICAN JOURNAL OF PHYSIOLOGY, 266 H1395-H1400 (1994)
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1994 |
LUMBERS ER, MENZIES RI, GIBSON KJ, TYNDALEBISCOE CH, 'LEVELS OF ACTIVE AND INACTIVE RENIN-LIKE ENZYMES IN PLASMA AND REPRODUCTIVE-TRACT OF THE PREGNANT WALLABY', AMERICAN JOURNAL OF PHYSIOLOGY, 266 R1353-R1358 (1994)
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Nova |
1994 |
GIBSON KJ, LUMBERS ER, 'CHANGES IN RENAL-FUNCTION AND BLOOD-VOLUME IN THE NEWBORN LAMB DELIVERED BY CESAREAN-SECTION', PEDIATRIC RESEARCH, 36 506-513 (1994)
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1994 |
Lumbers ER, Menzies RI, Gibson KJ, Tyndale-Biscoe CH, 'Levels of active and inactive reninlike enzymes in plasma and reproductive tract of the pregnant wallaby', AM.J.PHYSIOL., 266 (1994)
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1994 |
Nail BS, Lumbers ER, Stevens AD, 'The effect of fetal lung inflation on fetal heart rate', American Journal of Physiology - Heart and Circulatory Physiology, 266 (1994)
The effect on the fetal heart by inflating the fetal lungs with liquid or air while the animal was being maintained in utero by its normal placental circulation was investigated i... [more]
The effect on the fetal heart by inflating the fetal lungs with liquid or air while the animal was being maintained in utero by its normal placental circulation was investigated in 10 healthy, chronically catheterized fetal sheep of gestational age 126-137 days. It was found that initial attempts to inflate the lungs with volumes of air as small as 10 ml (i.e., with less than a predicted normal tidal volume) caused abrupt, powerful slowing of the fetal heart with, usually, an associated hypotension. Inflations with similarly small volumes of saline were ineffective. Atropine pretreatment abolished the cardiac slowing caused by the air inflations, indicating the operation of a neural reflex. An analysis of the pressure changes induced by the air and liquid inflations in airway, intrathoracic and intra-amniotic pressures showed that the cardiac slowing was primarily related to the level of mechanical stress applied across the fetal airway.
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1994 |
Lumbers ER, Menzies RI, Gibson KJ, Tyndale-Biscoe CH, 'Levels of active and inactive reninlike enzymes in plasma and reproductive tract of the pregnant wallaby', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 266 (1994)
Active and total (acid-activated) levels of a reninlike enzyme (hereafter called renin) were measured in plasma, tissues, and yolk sac fluid of pregnant and postpartum wallabies. ... [more]
Active and total (acid-activated) levels of a reninlike enzyme (hereafter called renin) were measured in plasma, tissues, and yolk sac fluid of pregnant and postpartum wallabies. Plasma active renin generated angiotensin I (ANG I) from sheep angiotensinogen at 14 ± 1.3 (SE) ng · ml-1 · h-1, whereas acid-activated renin generated ANG I at 33.3 ± 2.5 ng · ml-1 · h-1, i.e., 44.2 ± 3.7% of renin in plasma was active, and 58 ± 3.7% was inactive. Inactive renin levels were highest in pregnant animals (P = 0.05). Uterine renin was mainly inactive (95%); levels were 5.1 ± 1.1 times plasma levels. The levels of renin in nonpregnant uteri were the same as those in pregnant uteri from the same animals. Uterine renin levels did not change with gestation. Pooled acid-activated yolk sac fluid generated ANG I at low rates (0.7 and 1.6 ng · ml-1 · h-1); the acid-activated supernatant of a homogenate of pooled fetal membranes generated ANG I at 15 ng · g wet wt-1 · h-1. Yolk sac fluid was strikingly different in electrolyte composition from maternal plasma. Its lower osmolality suggests that the membranes separating it from maternal plasma have a low permeability to water. Thus, although eutherian and marsupial mammals diverged 136-164 million years ago, the wallaby, like many eutherian mammals, has inactive renin in blood, in the female reproductive tract, and in fetal membranes.
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1993 |
DAWES J, LUMBERS ER, 'LOW-MOLECULAR-WEIGHT DERMATAN SULFATE (DESMIN-370) DOES NOT CROSS THE OVINE PLACENTA', BRITISH JOURNAL OF HAEMATOLOGY, 84 90-94 (1993)
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1993 |
LUMBERS ER, BURRELL JH, MENZIES RI, STEVENS AD, 'THE EFFECTS OF A CONVERTING-ENZYME-INHIBITOR (CAPTOPRIL) AND ANGIOTENSIN-II ON FETAL RENAL-FUNCTION', BRITISH JOURNAL OF PHARMACOLOGY, 110 821-827 (1993)
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1993 |
GIBSON KJ, LUMBERS ER, 'THE ROLES OF ARGININE-VASOPRESSIN IN FETAL SODIUM-BALANCE AND AS A MEDIATOR OF THE EFFECTS OF FETAL STRESS', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 19 125-136 (1993)
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1992 |
LUMBERS ER, KINGSFORD NM, MENZIES RI, STEVENS AD, 'ACUTE EFFECTS OF CAPTOPRIL, AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, ON THE PREGNANT EWE AND FETUS', AMERICAN JOURNAL OF PHYSIOLOGY, 262 R754-R760 (1992)
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1992 |
GIBSON KJ, LUMBERS ER, 'MECHANISMS BY WHICH THE PREGNANT EWE CAN SUSTAIN INCREASED SALT AND WATER-SUPPLY TO THE FETUS', JOURNAL OF PHYSIOLOGY-LONDON, 445 569-579 (1992)
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1992 |
MOORE RS, LUMBERS ER, 'RENAL AND METABOLIC EFFECTS OF GLUCAGON IN THE FETUS', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 17 47-49 (1992)
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1992 |
STEVENSON KM, LUMBERS ER, 'EFFECTS OF INDOMETHACIN ON FETAL RENAL-FUNCTION, RENAL AND UMBILICOPLACENTAL BLOOD-FLOW AND LUNG LIQUID PRODUCTION', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 17 257-264 (1992)
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Nova |
1992 |
TANGALAKIS K, LUMBERS ER, MORITZ KM, TOWSTOLESS MK, WINTOUR EM, 'EFFECT OF CORTISOL ON BLOOD-PRESSURE AND VASCULAR REACTIVITY IN THE OVINE FETUS', EXPERIMENTAL PHYSIOLOGY, 77 709-717 (1992)
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1992 |
Lumbers ER, Kingsford NM, Menzies RI, Stevens AD, 'Acute effects of captopril, an angiotensin-converting enzyme inhibitor, on the pregnant ewe and fetus', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 262 (1992)
After control measurements had been made, 15 chronically catheterized pregnant ewes (gestational age 123-141 days) were given 15 mg of captopril intravenously followed by an infus... [more]
After control measurements had been made, 15 chronically catheterized pregnant ewes (gestational age 123-141 days) were given 15 mg of captopril intravenously followed by an infusion of 6 mg/h. These doses blocked the pressor responses of both ewes and fetuses to 5 µg of angiotensin I. After captopril, maternal mean arterial pressure fell from 94 ± 3.5 to 88 ± 3.6 (SE) mmHg (P < 0.0001) and pulse interval fell (P = 0.008). Maternal flow to the cotyledons fell from 766 ± 118 to 525 ± 77 ml/min (P = 0.002), as did flow to the remainder of the maternal placenta, i.e., the caruncles and their underlying myoendometrium (control flow 188 ± 35 ml/min, flow 10-15 min after captopril 166 ± 36.1 ml/min; P = 0.021). Flow to the rest of the myometrium did not change. Fetal arterial pressure fell from 46.9 ± 1.6 to 44.1 ± 1.6 mmHg (P < 0.009), and fetal placental blood flow fell from 639.9 ± 93.2 to 413.1 ± 53.9 ml/min (P = 0.025). Flow to the fetal membranes declined also, from 53.2 ± 6.5 to 35.6 ± 3.3 ml/min (P < 0.005). Maternal and fetal renal blood flows and fetal adrenal blood flows were unchanged. Fetal arterial PO2 was initially 19.5 ± 0.8 mmHg; after captopril, it was 17.7 ± 0.9 mmHg (P = 0.03). Fetal urine flow rate fell from 0.66 ± 0.08 ml/min to a nadir of 0.25 ± 0.08 ml/min (P < 0.0001) while urinary osmolality rose from 108 ± 5 mosmol/kgH2O to a maximum of 229 ± 42 mosmol/kgH2O at the end of the experiment (P = 0.001). Sodium excretion (P = 0.022) also declined from 15.8 ± 2.6 to 8.8 ± 1.7 µmol/min. It is concluded that captopril induces maternal hypotension and falls in maternal and fetal placental flows, which leads to changes in fetal blood gases and fetal renal function. However, there may also be direct effects of captopril on fetal renal function.
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1991 |
LUMBERS ER, MOORE RS, STEVENS AD, GIBSON KJ, 'CHANGES IN FETAL AND MATERNAL PLASMA-PROTEIN CONCENTRATION AND COLLOID OSMOTIC-PRESSURE WITH GESTATION', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 15 347-350 (1991)
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Nova |
1991 |
LUMBERS ER, KINGSFORD NM, MENZIES RI, 'THE RELATIONSHIPS BETWEEN FETAL AND MATERNAL PLACENTAL BLOOD FLOWS', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 16 125-132 (1991)
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1990 |
STEVENS AD, LUMBERS ER, 'EFFECTS OF REDUCED UTERINE BLOOD-FLOW ON FETAL CARDIOVASCULAR, RENAL, AND LUNG-FUNCTION', AMERICAN JOURNAL OF PHYSIOLOGY, 259 R1004-R1011 (1990)
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1990 |
KAIRAITIS K, LUMBERS ER, 'THE INFLUENCE OF ENDOGENOUS MINERALOCORTICOIDS ON THE COMPOSITION OF FETAL URINE', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 13 347-351 (1990)
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1990 |
LEADER LR, SMITH FG, LUMBERS ER, 'THE EFFECT OF ETHANOL ON HABITUATION AND THE CARDIOVASCULAR-RESPONSE TO STIMULATION IN FETAL SHEEP', EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY, 36 87-95
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1990 |
LUMBERS ER, 'EFFECTS ON SHEEP BLOOD-PRESSURE OF TREATMENT WITH ANGIOTENSIN, STEROIDS AND SALT', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 17 315-319 (1990)
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1990 |
ELBOURNE I, LUMBERS ER, HILL KJ, 'THE SECRETION OF ORGANIC-ACIDS AND BASES BY THE OVINE FETAL KIDNEY', EXPERIMENTAL PHYSIOLOGY, 75 211-221 (1990)
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Nova |
1990 |
Stevens AD, Lumbers ER, 'Effects of reduced uterine blood flow on fetal cardiovascular, renal, and lung function', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 259 (1990)
Uterine blood flow (UBF) was reduced for 1 h by partially occluding the maternal aorta below the renal arteries in seven pregnant ewes (gestation age 126-134 days). Fetuses became... [more]
Uterine blood flow (UBF) was reduced for 1 h by partially occluding the maternal aorta below the renal arteries in seven pregnant ewes (gestation age 126-134 days). Fetuses became hypoxic, acidemic, and hypercapnic. They developed hypertension (P < 0.005) and a bradycardia (P < 0.05). During restricted UBF, fetal hematocrit (Hct) rose (P < 0.005) and blood volume fell in five of seven fetuses. After release of constriction, fetal Hct fell, and blood volume rose by 7.5 ± 3.26% (P < 0.05) relative to control. During reduced UBF, lung liquid and urine flow rates fell (P < 0.025 and P < 0.05, respectively). After the occluder was released, Na excretion (which did not fall significantly during reduced UBF) increased (P < 0.05), and fractional reabsorption of Na fell (P < 0.05). Changes in fetal blood volume (FBV) were directly related to changes in maternal lower body flow (r = 0.47, P = 0.01, n = 33), and changes in fetal Hct were inversely related to maternal flow (r = -0.635, P = 0.001). Fetal urinary Na excretion per kilogram body weight was directly related to FBV per kilogram (r = 0.44, P = 0.005, n = 40), whereas fractional reabsorption of Na was inversely related to FBV per kilogram body wt (r = 0.48, P < 0.002, n = 39). It is concluded that reductions in UBF cause fetal hypoxemia and acidemia, which lead to changes in fetal cardiovascular function and in FBV. These changes lead to marked changes in fetal renal function and lung liquid flow and could account for the variability in urinary osmolality and Na excretion often seen in chronically catheterized fetal sheep.
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1989 |
LEADER LR, SMITH FG, LUMBERS ER, STEVENS AD, 'EFFECT OF HYPOXIA AND CATECHOLAMINES ON THE HABITUATION RATES OF CHRONICALLY CATHETERIZED OVINE FETUSES', BIOLOGY OF THE NEONATE, 56 218-227 (1989)
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1989 |
SMITH FG, LUMBERS ER, 'COMPARISON OF RENAL-FUNCTION IN TERM FETAL SHEEP AND NEWBORN LAMBS', BIOLOGY OF THE NEONATE, 55 309-316 (1989)
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Nova |
1989 |
LUMBERS ER, SMITH FG, 'MEASUREMENT OF NET SODIUM-INTAKE BY THE OVINE FETUS WITH ESOPHAGEAL LIGATION', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 16 859-866 (1989)
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1989 |
KINGSFORD NM, LUMBERS ER, 'EFFECTS OF AUTONOMIC BLOCKADE ON THE HYPERTENSIVE RESPONSE OF THE FETUS TO HYPEROSMOLALITY', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 16 873-883 (1989)
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1988 |
Smith FG, Lumbers ER, 'Effects of maternal hyperglycemia on fetal renal function in sheep', American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 255 (1988)
The effects of maternal hyperglycemia on fetal renal function were investigated in 10 chronically catheterized fetal sheep after the infusion of 100 g of glucose into the ewe over... [more]
The effects of maternal hyperglycemia on fetal renal function were investigated in 10 chronically catheterized fetal sheep after the infusion of 100 g of glucose into the ewe over 30 min. Fetal blood glucose levels rose (P < 0.001) within 15 min of completing the glucose infusion from 15.75 ± 2.8 to 195.4 ± 18 (SE) mg/dl (n = 10). There was a significant increase in fetal glomerular filtration rate (P < 0.005) from 2.73 ± 0.41 to 3.65 ± 0.40 (SE) ml/min (n = 10) within 1.5 h of the infusion of glucose into the ewe. Urine flow rate increased from 0.38 ± 0.06 to 0.63 ± 0.12 (SE) ml/min (n = 10, P < 0.001), and sodium excretion increased from 18.42 ± 7.21 to 38.4 ± 13.7 (SE) µmol/min (n = 10, P < 0.002) within 2.5 h of the infusion of glucose into the ewe. The fraction of the filtered load that was excreted (urine flow rate divided by glomerular filtration rate) also increased (P < 0.01) as did the fraction of the osmolar load (P < 0.002). Glycosuria occurred in all fetuses within 30 min of the infusion of glucose into the ewe, and glucose excretion reached 26.16 ± 12.36 (SE) µg/min (n = 8) after 1.5 h. These findings of diuresis, natriuresis, and glycosuria in response to hyperglycemia are evidence that an increased delivery of fluid into the amniotic cavity might occur after a rise in fetal plasma glucose levels.
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Nova |
1988 |
SMITH FG, LUMBERS ER, 'EFFECTS OF MATERNAL HYPERGLYCEMIA ON FETAL RENAL-FUNCTION IN SHEEP', AMERICAN JOURNAL OF PHYSIOLOGY, 255 F11-F14 (1988)
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1988 |
LEADER LR, STEVENS AD, LUMBERS ER, 'MEASUREMENT OF FETAL RESPONSES TO VIBROACOUSTIC STIMULI - HABITUATION IN FETAL SHEEP', BIOLOGY OF THE NEONATE, 53 73-85 (1988)
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Nova |
1988 |
LUMBERS ER, HILL KJ, BENNETT VJ, 'PROXIMAL AND DISTAL TUBULAR ACTIVITY IN CHRONICALLY CATHETERIZED FETAL SHEEP COMPARED WITH THE ADULT', CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 66 697-702 (1988)
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1988 |
KESBY GJ, LUMBERS ER, 'THE EFFECTS OF METABOLIC-ACIDOSIS ON RENAL-FUNCTION OF FETAL SHEEP', JOURNAL OF PHYSIOLOGY-LONDON, 396 65-74 (1988)
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Nova |
1988 |
HILL KJ, LUMBERS ER, ELBOURNE I, 'THE ACTIONS OF CORTISOL ON FETAL RENAL-FUNCTION', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 10 85-96 (1988)
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1988 |
SMITH FG, LUMBERS ER, 'CHANGES IN RENAL-FUNCTION FOLLOWING DELIVERY OF THE LAMB BY CESAREAN-SECTION', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 10 145-148 (1988)
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1988 |
HILL KJ, LUMBERS ER, 'RENAL-FUNCTION IN ADULT AND FETAL SHEEP', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 10 149-159 (1988)
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Nova |
1987 |
LUMBERS ER, STEVENS AD, 'THE EFFECTS OF FRUSEMIDE, SARALASIN AND HYPOTENSION ON FETAL PLASMA-RENIN ACTIVITY AND ON FETAL RENAL-FUNCTION', JOURNAL OF PHYSIOLOGY-LONDON, 393 479-490 (1987)
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Nova |
1987 |
SMITH FG, LUMBERS ER, 'THE EFFECT OF MATERNAL HYPERGLYCEMIA ON ACID-BASE-BALANCE AND LUNG LIQUID PRODUCTION IN THE FETAL SHEEP', PEDIATRIC RESEARCH, 22 355-359 (1987)
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Nova |
1987 |
LUMBERS ER, 'RENAL-FUNCTION DURING INTRAUTERINE LIFE', NEWS IN PHYSIOLOGICAL SCIENCES, 2 220-223 (1987)
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1986 |
Lumbers ER, 'Understanding the effects of drugs in pregnancy', Current Therapeutics, 27 15-27 (1986) |
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Nova |
1986 |
KESBY GJ, LUMBERS ER, 'FACTORS AFFECTING RENAL HANDLING OF SODIUM, HYDROGEN-IONS, AND BICARBONATE BY THE FETUS', AMERICAN JOURNAL OF PHYSIOLOGY, 251 F226-F231 (1986)
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1986 |
SMITH FG, LUMBERS ER, KESBY GJ, 'THE RENAL RESPONSE TO THE INGESTION OF FLUID BY THE FETAL SHEEP', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 8 259-266 (1986)
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1986 |
STEVENS AD, LUMBERS ER, 'EFFECT ON MATERNAL AND FETAL RENAL-FUNCTION AND PLASMA-RENIN ACTIVITY OF A HIGH SALT INTAKE BY THE EWE', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 8 267-275 (1986)
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1986 |
LUMBERS ER, MCCLOSKEY DI, POTTER EK, COURTICE GP, 'CARDIAC VAGAL ACTION DURING HYPOXIA IN ADULT AND FETAL SHEEP', JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM, 16 23-34 (1986)
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1985 |
Caine AC, Lumbers ER, Reid IA, 'The effects and interactions of angiotensin and vasopressin on the heart of unanaesthetized sheep.', The Journal of Physiology, 367 1-11 (1985)
The effects of infusions of angiotensin and vasopressin, in stepwise concentrations, on the cardiac baroreflex and on cardiac output were studied in seven adult unanaesthetized sh... [more]
The effects of infusions of angiotensin and vasopressin, in stepwise concentrations, on the cardiac baroreflex and on cardiac output were studied in seven adult unanaesthetized sheep and compared with those obtained with infusions of phenylephrine. Six animals were treated with the beta-adrenoceptor blocking drug, propranolol (in order to inhibit the effects of the sympathetic nervous system on the heart). One animal was not treated with propranolol. In those animals in which arterial pressure increased during infusion of vasopressin, the slope of the systolic pressure-pulse interval relation was greater than that seen when phenylephrine was used to increase arterial pressure. Compared with the cardiac response to pressor doses of phenylephrine, infusions of angiotensin were associated with a lesser degree of cardiac slowing and a lesser reduction in cardiac output. The effects of combined infusions of angiotensin and vasopressin on the cardiac baroreflex were studied. In five sheep which were infused with a pressor dose of angiotensin (1.1 microgram/min), the stimulatory effect of vasopressin (1.0 u./min) on pulse interval and its depressant effect on cardiac output were attenuated. In seven sheep infused with 0.5 u./min of vasopressin, I.V. infusion of angiotensin (0.2-5.0 micrograms), produced a progressive decrease in pulse interval and increase in cardiac output as the dose was increased. Therefore, angiotensin can offset the cardioinhibitory effects of vasopressin. Since cardiac sympathetic activity was blocked and neither drug has any direct chronotropic effect on the heart, it would appear that these interactions between the two drugs affect the cardiac vagus either at a peripheral or central level. © 1985 The Physiological Society
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1985 |
LUMBERS ER, SMITH FG, STEVENS AD, 'MEASUREMENT OF NET TRANS-PLACENTAL TRANSFER OF FLUID TO THE FETAL SHEEP', JOURNAL OF PHYSIOLOGY-LONDON, 364 289-299 (1985)
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1985 |
CAINE AC, LUMBERS ER, REID IA, 'THE EFFECTS AND INTERACTIONS OF ANGIOTENSIN AND VASOPRESSIN ON THE HEART OF UNANESTHETIZED SHEEP', JOURNAL OF PHYSIOLOGY-LONDON, 367 1-11 (1985)
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1985 |
STEVENS AD, LUMBERS ER, 'THE EFFECT OF MATERNAL FLUID INTAKE ON THE VOLUME AND COMPOSITION OF FETAL URINE', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 7 161-166 (1985)
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1985 |
POTTER EK, PARKER P, CAINE AC, LUMBERS ER, 'POTENTIATION OF CARDIAC VAGAL ACTION BY COLD', CLINICAL SCIENCE, 68 165-169 (1985)
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1984 |
COURTICE GP, KWONG TE, LUMBERS ER, POTTER EK, 'EXCITATION OF THE CARDIAC VAGUS BY VASOPRESSIN IN MAMMALS', JOURNAL OF PHYSIOLOGY-LONDON, 354 547-556 (1984)
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1984 |
LUMBERS ER, 'A BRIEF REVIEW OF FETAL RENAL-FUNCTION', JOURNAL OF DEVELOPMENTAL PHYSIOLOGY, 6 1-10 (1984)
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1983 |
LUMBERS ER, POTTER EK, 'INHIBITION OF THE VAGAL COMPONENT OF THE BARORECEPTOR-CARDIOINHIBITORY REFLEX BY ANGIOTENSIN-III IN DOGS AND SHEEP', JOURNAL OF PHYSIOLOGY-LONDON, 336 83-89 (1983)
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1983 |
LUMBERS ER, STEVENS AD, 'CHANGES IN FETAL RENAL-FUNCTION IN RESPONSE TO INFUSIONS OF A HYPEROSMOTIC SOLUTION OF MANNITOL TO THE EWE', JOURNAL OF PHYSIOLOGY-LONDON, 343 439-446 (1983)
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1982 |
LUMBERS ER, POTTER EK, 'THE EFFECTS OF VASOACTIVE PEPTIDES ON THE CAROTID CARDIAC BAROREFLEX', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 45-49 (1982)
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1981 |
Stevens AD, Lumbers ER, 'The relationship between plasma renin activity and renal electrolyte excretion in the fetal sheep', Journal of Developmental Physiology, 3 101-110 (1981)
In eight fetal sheep the factors influencing renal sodium excretion were determined and related to the activity of the renin-angiotensin system. There was a direct relationship be... [more]
In eight fetal sheep the factors influencing renal sodium excretion were determined and related to the activity of the renin-angiotensin system. There was a direct relationship between glomerular filtration rate (GFR) and the amount of sodium reabsorbed (P <0.001) suggesting that glomerular tubular balance plays an important role in regulation of fetal sodium excretion. There was also a direct relationship between GFR and urinary sodium excretion (P <0.05). Since the percentage of the filtered sodium load that was reabsorbed was inversely related to the urinary Na/K ratio, (P <0.001), the distal convoluted tubule is actively involved in the regulation of renal sodium excretion. There was no relationship between plasma renin activity and plasma sodium, and plasma osmolality or mean arterial pressure. There was however an inverse relationship between urinary sodium excretion and plasma renin activity, similar to that seen in adult animals (Vander & Miller, 1964) and between log plasma renin activity and GFR (P <0.001). These experiments do not distinguish between a possible effect of angiotensin on GFR and hence renal sodium excretion, and the possible effects of a variable GFR on distal tubular sodium delivery and hence renin secretion. However they do show that the fetal renin-angiotensin system like the adult renin-angiotensin system is closely linked to those renal factors that influence renal sodium excretion.
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1981 |
ALEXANDER IE, LUMBERS ER, 'THE EFFECTS OF ANGIOTENSIN ON RESPIRATORY PATTERNS OF ANESTHETIZED DOGS', RESPIRATION PHYSIOLOGY, 46 261-270 (1981)
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1981 |
LEE WB, LUMBERS ER, 'ANGIOTENSIN AND THE CARDIAC BAROREFLEX RESPONSE TO PHENYLEPHRINE', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 8 109-117 (1981)
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1981 |
LUMBERS ER, REID IA, 'THE CARDIOVASCULAR EFFECTS OF INTRAVERTEBRAL ANGIOTENSIN-II BEFORE AND AFTER TREATMENT WITH CLONIDINE', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 8 531-535 (1981)
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1980 |
Lumbers ER, Stevens AD, Alexander G, Stevens D, 'The cardiovascular responses of conscious newborn lambs treated in utero with 6-hydroxydopamine', Journal of Developmental Physiology, 2 139-149 (1980)
Fourteen fetal sheep were treated in utero with a single intramuscular injection or three to four injections or three to four injections of 6-hydroxydopamine. After birth the card... [more]
Fourteen fetal sheep were treated in utero with a single intramuscular injection or three to four injections or three to four injections of 6-hydroxydopamine. After birth the cardiovascular responses of these lambs to adrenergic drugs were studied and compared with the cardiovascular responses of untreated newborn lambs. Lambs which received three to four injections of 6-hydroxydopamine were more sensitive to the pressor actins of noradrenaline and phenylephrine than were control lambs or lambs which received a single injection of 6-hydroxydopamine. The supersensitivity to noradrenaline persisted in multiple treatment lambs until at least 5 months of age. Lambs which received multiple injections of 6-hydroxydopamine were also subsensitive to the pressor action of tyramine. The sensitivity to the pressor actions of noradrenaline and phenylephrine in lambs which received a single injection of 6-hydroxydopamine lay between that of control and multiple treatment groups. Despite the pharmacological evidence of impairment of sympathetic innervation of peripheral blood vessels plus a lack of responsiveness of these lambs to a-adrenergic blockade with phentolamine, treated lambs had arterial pressures and heart rates similar to control lambs. As well, treated lambs showed no impairment in their ability to reflexly regulate heart rate in response to changes in arterial pressure, which is consistent with the recently reported vagal control of the cardiac baroreceptor reflex.
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1980 |
LEE WB, ISMAY MJ, LUMBERS ER, 'MECHANISMS BY WHICH ANGIOTENSIN-II AFFECTS THE HEART-RATE OF THE CONSCIOUS SHEEP', CIRCULATION RESEARCH, 47 286-292 (1980)
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1980 |
LUMBERS ER, STEVENS AD, 'FACTORS INFLUENCING GLOMERULAR-FILTRATION RATE IN THE FETAL LAMB', JOURNAL OF PHYSIOLOGY-LONDON, 298 P28-P29 (1980)
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1979 |
Ismay MJ, Lumbers ER, Stevens AD, 'The action of angiotensin II on the baroreflex response of the conscious ewe and the conscious fetus.', The Journal of Physiology, 288 467-479 (1979)
1. In conscious non-pregnant and pregnant ewes and in chronic fetal lamb preparations, the beat by beat relationship between pulse interval and systolic pressure was studied durin... [more]
1. In conscious non-pregnant and pregnant ewes and in chronic fetal lamb preparations, the beat by beat relationship between pulse interval and systolic pressure was studied during acute elevations in arterial pressure induced by phenylephrine. Baroreflex sensitivity, which was defined as the slope of the pressure-pulse interval relationship when phenylephrine was used to raise pressure, was abolished by atropine and increased by propranolol. Baroreflex sensitivity was less in pregnant ewes and in foetal lambs compared with non-pregnant ewes. 2. These findings suggest that the vagus nerve is responsible for the reflex bradycardia that occurs in the foetus and the ewe when arterial pressure is increased. 3. In both fetal and adult sheep, actue hypertension due to I.V. injection of angiotensin II was not associated with a consistent and progressive bradycardia, such as was seen with acute hypertension caused by phenylephrine. Angiotensin II has no direct chronotropic effect on heart rate in either the adult or the fetus. 4. No linear relationship between arterial pressure and pulse interval was seen when angiotensin II was used to raise pressure in sheep which were treated with propranolol. Therefore the lack of cardiac slowing with pressor doses of angiotensin II was not due to concomitant activation of the sympathoadrenal system. 5. It is concluded that in both fetal and adult sheep angiotensin II reduces the increase in vagal tone which is responsible for slowing of heart rate in response to acute rises in arterial pressure. © 1979 The Physiological Society
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1979 |
LUMBERS ER, LEWES JL, 'ACTIONS OF VASOACTIVE DRUGS ON FETAL AND MATERNAL PLASMA-RENIN ACTIVITY', BIOLOGY OF THE NEONATE, 35 23-32 (1979)
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1979 |
ISMAY MJA, LUMBERS ER, STEVENS AD, 'ACTION OF ANGIOTENSIN-II ON THE BAROREFLEX RESPONSE OF THE CONSCIOUS EWE AND THE CONSCIOUS FETUS', JOURNAL OF PHYSIOLOGY-LONDON, 288 467-479 (1979)
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1979 |
LUMBERS ER, MCCLOSKEY DI, POTTER EK, 'INHIBITION BY ANGIOTENSINII OF BARORECEPTOR-EVOKED ACTIVITY IN CARDIAC VAGAL EFFERENT NERVES IN THE DOG', JOURNAL OF PHYSIOLOGY-LONDON, 294 69-80 (1979)
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1979 |
POTTER EK, LUMBERS ER, MCCLOSKEY DI, 'INHIBITION OF CARDIAC VAGAL EFFERENT NERVE ACTIVITY BY INTRAVENOUS ADMINISTRATION OF ANGIOTENSIN-II', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 6 675-676 (1979) |
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1978 |
LUMBERS ER, REID GC, 'ACTIONS OF VASOACTIVE COMPOUNDS IN FETUS AND EFFECT OF PERFUSION THROUGH PLACENTA ON THEIR BIOLOGICAL-ACTIVITY', AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE, 56 11-24 (1978)
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1977 |
LUMBERS ER, LEELEWES J, 'EFFECTS OF BETA AND ALPHA ADRENERGIC COMPOUNDS ON RELEASE OF RENIN FROM FETAL KIDNEY', AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE, 7 446-446 (1977) |
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1977 |
LUMBERS ER, REID GC, 'EFFECTS OF VAGINAL DELIVERY AND CESAREAN-SECTION ON PLASMA-RENIN ACTIVITY AND ANGIOTENSIN-II LEVELS IN HUMAN UMBILICAL-CORD BLOOD', BIOLOGY OF THE NEONATE, 31 127-134 (1977)
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1974 |
Pipkin FB, Lumbers ER, Mott JC, 'Proceedings: Effects of hypoxia on maternal and foetal renin and angiotensin II in sheep.', Journal of Physiology, 238 (1974) |
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1974 |
PIPKIN FB, LUMBERS ER, MOTT JC, 'PLASMA-RENIN AND ANGIOTENSIN-II IN CONSCIOUS PREGNANT EWES AND THEIR LAMBS', JOURNAL OF PHYSIOLOGY-LONDON, 237 P52-P53 (1974)
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1974 |
BROUGHTONPIPKIN F, KIRKPATRICK SM, LUMBERS ER, MOTT JC, 'RENIN AND ANGIOTENSIN-LIKE LEVELS IN FETAL, NEWBORN AND ADULT SHEEP', JOURNAL OF PHYSIOLOGY-LONDON, 241 575-588 (1974)
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1974 |
BROUGHTONPIPKIN F, LUMBERS ER, MOTT JC, 'FACTORS INFLUENCING PLASMA-RENIN AND ANGIOTENSIN-II IN CONSCIOUS PREGNANT EWE AND ITS FETUS', JOURNAL OF PHYSIOLOGY-LONDON, 243 619-636 (1974)
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1973 |
Lumbers ER, 'Proceedings: Renin and angiotensin II of extrarenal origin in the plasma of female rabbits.', Journal of Physiology, 234 (1973)
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1972 |
BONNIN JM, LUMBERS ER, HODGE RL, 'RENIN-SECRETING RENAL TUMOR ASSOCIATED WITH HYPERTENSION', AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE, 2 178-& (1972)
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1972 |
MORRIS BJ, LUMBERS ER, 'ACTIVATION OF RENIN IN HUMAN AMNIOTIC-FLUID BY PROTEOLYTIC-ENZYMES', BIOCHIMICA ET BIOPHYSICA ACTA, 289 385-391 (1972)
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1972 |
CLEZY TM, FOY BN, HODGE RL, LUMBERS ER, 'ORAL-CONTRACEPTIVES AND HYPERTENSION EPIDEMIOLOGICAL SURVEY', BRITISH HEART JOURNAL, 34 1238-1243 (1972)
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1972 |
LUMBERS ER, TRIMPER CE, 'RELEASE OF RENIN INTO PERIPHERAL CIRCULATION OF EWE AND FETUS, FOLLOWING ADMINISTRATION OF FRUSEMIDE, A NATRIURETIC AGENT', JOURNAL OF PHYSIOLOGY-LONDON, 225 P34-& (1972)
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1972 |
PIPKIN FB, LUMBERS ER, MOTT JC, 'BIRTH AND ANGIOTENSIN II-LIKE ACTIVITY IN LAMBS', JOURNAL OF PHYSIOLOGY-LONDON, 226 P109-+ (1972)
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1972 |
TRIMPER CE, LUMBERS ER, 'RENIN-ANGIOTENSIN SYSTEM IN FETAL LAMBS', PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 336 1-& (1972)
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1972 |
SKINNER SL, SYMONDS EM, LUMBERS ER, 'ANALYSIS OF CHANGES IN RENIN-ANGIOTENSIN SYSTEM DURING PREGNANCY', CLINICAL SCIENCE, 42 479-& (1972)
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1971 |
LUMBERS ER, 'ACTIVATION OF RENIN IN HUMAN AMNIOTIC FLUID BY LOW PH', ENZYMOLOGIA, 40 329-+ (1971)
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1970 |
Lim YL, Lumbers ER, Walters WAW, Whelan RF, 'EFFECTS OF OESTROGENS ON THE HUMAN CIRCULATION', BJOG: An International Journal of Obstetrics & Gynaecology, 77 349-355 (1970)
The naturally occurring oestrogens, oestrone and oestriol, were given by intraarterial infusion into the brachial artery and by intravenous injection. No changes in blood flow thr... [more]
The naturally occurring oestrogens, oestrone and oestriol, were given by intraarterial infusion into the brachial artery and by intravenous injection. No changes in blood flow through the hand or forearm were observed with either route of administration. Intravenous injection resulted in a significant rise in blood pressure but no significant changes in heart rate or limb vascular resistance. It is suggested that this rise in blood pressure may be due to a direct action of the hormones on the heart. Copyright © 1970, Wiley Blackwell. All rights reserved
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1970 |
Lim YL, Lumbers ER, Walters WA, Whelan RF, 'Effects of oestrogens on the human circulation.', The Journal of obstetrics and gynaecology of the British Commonwealth, 77 349-355 (1970)
The naturally occurring oestrogens, oestrone and oestriol, were given by intraarterial infusion into the brachial artery and by intravenous injection. No changes in blood flow thr... [more]
The naturally occurring oestrogens, oestrone and oestriol, were given by intraarterial infusion into the brachial artery and by intravenous injection. No changes in blood flow through the hand or forearm were observed with either route of administration. Intravenous injection resulted in a significant rise in blood pressure but no significant changes in heart rate or limb vascular resistance. It is suggested that this rise in blood pressure may be due to a direct action of the hormones on the heart. Copyright © 1970, Wiley Blackwell. All rights reserved
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1970 |
LUMBERS ER, 'PERIPHERAL VASCULAR REACTIVITY TO ANGIOTENSIN AND NORADRENALINE IN PREGNANT AND NON-PREGNANT WOMEN', AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE, 48 493-& (1970)
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1970 |
LUMBERS ER, WHELAN RF, 'TACHYPHYLAXIS TO ANGIOTENSIN IN MAN', CARDIOVASCULAR RESEARCH, 4 312-+ (1970)
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1969 |
LUMBERS ER, SKINNWR SL, 'OCCURRENCE AND ASSAY OF RENIN IN HUMAN URINE', AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE, 47 251-& (1969)
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1969 |
LUMBERS ER, SKINNER SL, 'OBSERVATIONS ON ORIGIN OF RENIN IN HUMAN URINE', CIRCULATION RESEARCH, 24 689-& (1969)
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1969 |
SKINNER SL, LUMBERS ER, SYMONDS EM, 'ALTERATION BY ORAL CONTRACEPTIVES OF NORMAL MENSTRUAL CHANGES IN PLASMA RENIN ACTIVITY CONCENTRATION AND SUBSTRATE', CLINICAL SCIENCE, 36 67-& (1969)
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1968 |
SKINNER SL, LUMBERS ER, SYMONDS EM, 'RENIN CONCENTRATION IN HUMAN FETAL AND MATERNAL TISSUES', AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 101 529-& (1968)
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