Hemodynamic Parameters During Normal and Hypertensive Pregnancy in Rats: Evaluation of Renal Salt and Water Transporters

Np, Abreu; Tardin, Joisse Caria Barboza Monerat; Boim, Mirian Aparecida; Campos, Rui; Bergamaschi, Cássia T.; Schor, Nestor

doi:10.1080/10641950701825887

Cited by 13 publications

(13 citation statements)

References 42 publications

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“…The observed down-regulation of AQP2 mRNA and protein expression during pregnancy is in direct contrast to evidence published previously demonstrating a pregnancy-related up-regulation of AQP2 in renal papillae [44,45]. Segmental differences in aquaporin protein expression in the kidney have been reported by other groups.…”

Section: Discussioncontrasting

confidence: 91%

The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins

Cornock

Langley‐Evans

Mobasheri

et al. 2010

Reprod Biol Endocrinol

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BackgroundMaternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma volume expansion. The study focused on expression of renal angiotensin receptors (ATR) and vasopressin-related aquaporins (AQP), hypothesising that an alteration in the balance of these proteins would be associated with pregnancy per se and with compromised plasma volume expansion in rats fed a low-protein diet.MethodsFemale Wistar rats were mated and fed a control (18% casein) or low-protein (9% casein) diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point) for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle.ResultsAs expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT2R protein expression was observed in low-protein fed animals alongside a decrease in creatinine clearance.ConclusionRegulatory systems involved in the pregnancy-induced plasma volume expansion are susceptible to the effects of maternal protein restriction.

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Section: Discussioncontrasting

confidence: 91%

The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins

Cornock

Langley‐Evans

Mobasheri

et al. 2010

Reprod Biol Endocrinol

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“…4) and also indicate that the larger transport capacity in the distal nephron of the female kidney renders women better equipped to handle (i.e., retain a significantly more of) the larger filtered load in pregnancy. Nevertheless, to completely compensate for the heightened load in pregnancy, further alternations in tubular transport are required [32,45,46].…”

Section: Discussionmentioning

confidence: 99%

“…Taken together, these simulations indicate that tubular hypertrophy, activation of reserve NHE3 capacity, and the higher (baseline) distal transport capacity together can attenuate the excessive natriuresis, diuresis, and kaliuresis that is predicted to arise due to hemodynamics changes similar to those observed in pregnancy. However, to achieve baseline urine output and excretion, additional changes are required, including transport adaptation along the distal segments [32].…”

Section: Sex Differences In Segmental Transport Under Baseline Conditmentioning

confidence: 99%

Sex Differences in Solute and Water Handling in the Human Kidney: Modeling and Functional Implications

McDonough

2021

Preprint

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Besides the excretion of metabolic wastes, the kidneys regulate homeostasis of electrolytes, pH, metabolites, volume and blood pressure. Sex differences in kidney function and blood pressure have been widely described across many species. Immunoblot analysis has revealed that the kidney of a female rat is not simply a smaller version of a male kidney. Rather, male and female rat kidneys exhibit dimorphic patterns of transporter expression and salt handling, the functional implications of which have been analyzed in a series of previously published modeling studies of rat kidney function. In the present study, we extend the analysis to the human kidney: we developed sex-specific models of solute and water transport in the human kidney, and identified epithelial transport parameters, consistent with patterns found in male and female rats, that yield urine output and excretion rates consistent with known human values. The model predicts that the lower sodium hydrogen exchanger 3 (NHE3) activity in women reduces the fractional reabsorption of Na+, K+, Cl-, and water along the proximal tubule, compared to men, and that the larger load on the distal nephron can be handled by enhanced activities in key Na+ transporter such as epithelial sodium channel (ENaC) and sodium chloride cotransporter (NCC) in women. Model simulations further indicate that the larger distal transport capacity and proximal transport reserve may better prepare women for elevated demands of pregnancy and lactation. The larger distal transport capacity may also contribute to reduced efficacy of angiotensin converting enzyme inhibitors to lower blood pressure in women.

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“…Normal pregnancy is characterized by increased blood volume, which is a fundamental requirement for adequate blood supply to the fetus. The expansion of the extracellular volume is primarily determined by renal sodium and water retention mediated by the upregulation of the water channel AQP2 [ 52 ] and the main sodium tubular transporters [ 7 ]. Indeed, in the present study we observed an upregulation of the NHE 3 and AQP2 mRNAs, suggesting they play a role in the sodium and water reabsorption in the control P group.…”

Section: Discussionmentioning

confidence: 99%

“…Pregnancy also imposes a necessary expansion of the extracellular volume (ECV) by sodium and water retention via mechanisms involving changes in the expression of tubular transporters. We recently demonstrated that the expression of renal transporters including the Na-Cl and Na-K-2Cl cotransporters, Na-H exchanger, and aquaporin 2 is increased during pregnancy in rats [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats

et al. 2016

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Pregnancy is characterized by maternal systemic and intrarenal vasodilation, leading to increases in the renal plasma flow (RPF) and glomerular filtration rate (GFR). These responses are mainly mediated by nitric oxide (NO) and relaxin. The impact of cigarette smoking on the maternal adaptations to pregnancy is unclear. Here we evaluated the effects of chronic exposure to nicotine on systemic and intrarenal parameters in virgin (V) and 14-day pregnant (P) Wistar rats. V and P groups received saline or nicotine (6 mg·kg-1·day-1) respectively, via osmotic minipumps for 28 days, starting 14 days before pregnancy induction. Nicotine induced a 10% increase in blood pressure in the V group and minimized the characteristic pregnancy-induced hypotension. Renal sympathetic nerve activity (rSNA) and baroreflex sensitivity were impaired by nicotine mainly in the P group, indicating that the effect of nicotine on blood pressure was not mediated by nervous system stimulation. Nicotine had no effect on GFR in the V rats but reduced GFR of the P group by 30%. Renal expression of sodium and water transporters was downregulated by nicotine, resulting in increased fractional sodium excretion mainly in the P group, suggesting that nicotine compromised the sodium and water retention required for normal gestation. There was a reduction in the expression of inducible NO synthase (iNOS) in both the kidney tissue and renal artery, as well as in the expression of the relaxin receptor (LGR7). These results clearly show that nicotine induced deleterious effects in both virgin and pregnant animals, and abolished the maternal capacity to adapt to pregnancy.

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Hemodynamic Parameters During Normal and Hypertensive Pregnancy in Rats: Evaluation of Renal Salt and Water Transporters

Abstract: Our results suggest that tubule transporter variants may mediate the hemodynamic adaptations seen during pregnancy, although we cannot rule out the hypothesis that other factors are also mediating hemodynamic changes.

Cited by 13 publications

References 42 publications

The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins

The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins

Sex Differences in Solute and Water Handling in the Human Kidney: Modeling and Functional Implications

Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats

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