Pregnant Wistar-Kyoto Research Articles

Pregnancy-associated changes in urinary uromodulin excretion in chronic hypertension

BackgroundPregnancy involves major adaptations in renal haemodynamics, tubular, and endocrine functions. Hypertensive disorders of pregnancy are a leading cause of maternal mortality and morbidity. Uromodulin is a nephron-derived protein that is associated with hypertension and kidney diseases. Here we study the role of urinary uromodulin excretion in hypertensive pregnancy.MethodsUrinary uromodulin was measured by ELISA in 146 pregnant women with treated chronic hypertension (n = 118) and controls (n = 28). We studied non-pregnant and pregnant Wistar Kyoto and Stroke Prone Spontaneously Hypertensive rats (n = 8/strain), among which a group of pregnant Stroke–Prone Spontaneously Hypertensive rats was treated with either nifedipine (n = 7) or propranolol (n = 8).ResultsIn pregnant women, diagnosis of chronic hypertension, increased maternal body mass index, Black maternal ethnicity and elevated systolic blood pressure at the first antenatal visit were significantly associated with a lower urinary uromodulin-to-creatinine ratio. In rodents, pre-pregnancy urinary uromodulin excretion was twofold lower in Stroke-Prone Spontaneously Hypertensive rats than in Wistar Kyoto rats. During pregnancy, the urinary uromodulin excretion rate gradually decreased in Wistar Kyoto rats (a twofold decrease), whereas a 1.5-fold increase was observed in Stroke-Prone Spontaneously Hypertensive rats compared to pre-pregnancy levels. Changes in uromodulin were attributed by kidney injury in pregnant rats. Neither antihypertensive changed urinary uromodulin excretion rate in pregnant Stroke-Prone Spontaneously Hypertensive rats.ConclusionsIn summary, we demonstrate pregnancy-associated differences in urinary uromodulin: creatinine ratio and uromodulin excretion rate between chronic hypertensive and normotensive pregnancies. Further research is needed to fully understand uromodulin physiology in human pregnancy and establish uromodulin’s potential as a biomarker for renal adaptation and renal function in pregnancy.Graphical abstract

Gene Dysregulation in the Adult Rat Paraventricular Nucleus and Amygdala by Prenatal Exposure to Dexamethasone.

Fetal programming is the concept that maternal stressors during critical periods of fetal development can alter offspring phenotypes postnatally. Excess glucocorticoids can interact with the fetus to effect genetic and epigenetic changes implicated in adverse developmental outcomes. The present study investigates how chronic exposure to the synthetic glucocorticoid dexamethasone during late gestation alters the expression of genes related to behavior in brain areas relevant to the regulation and function of the hypothalamic–pituitary–adrenal axis. Pregnant Wistar Kyoto rats received subcutaneous injections of dexamethasone (100 μg/kg) daily from gestational day 15–21 or vehicle only as sham controls. The amygdala and paraventricular nucleus (PVN) were micro-punched to extract mRNA for reverse transcription and quantitative polymerase chain reaction for the analysis of the expression of specific genes. In the PVN, the expression of the glucocorticoid receptor NR3C1 was downregulated in female rats in response to programming. The expression of CACNA1C encoding the Cav1.2 pore subunit of L-type voltage-gated calcium channels was downregulated in male and female rats prenatally exposed to dexamethasone. Collectively, the results suggest that prenatal exposure to elevated levels of glucocorticoids plays a role in the dysregulation of the hypothalamic–pituitary–adrenal axis and potentially learning and memory by altering the expression of specific genes within the amygdala and PVN.

Abstract P232: Pregnancy Induced Changes In Urinary Uromodulin Excretion In Normotensive And Chronic Hypertensive Rodent Models

Hypertensive disorders complicate 1-4% of pregnancies and are the leading cause of maternal death. Pregnancy involves major adaptions in renal hemodynamics, tubular and endocrine functions. Uromodulin (UMOD) is a renal protein that plays a role in renal sodium and divalent cation transport and is associated with hypertension and kidney diseases. We aimed to understand the role of blood pressure (BP) in urinary UMOD excretion during pregnancy. Pregnant Wistar Kyoto (WKY) and Stroke Prone Spontaneously Hypertensive (SHRSP) rats (n=8) were studied for 18.5 gestational days (GD). A group of pregnant SHRSP were treated with the beta-blocker propranolol (100mg/kgBW/day; n=8) and the calcium channel blocker nifedipine (25mg/kgBW/day; n=7) from GD 0.5. Systolic BP (SBP; tail cuff plethysmography), urine and plasma characteristic were monitored at baseline, GD3.5, GD12.5 and GD 18.5. UMOD concentration were measured in 24hr urine with ELISA. Pregnant SHRSP were hypertensive throughout the gestation compared to WKY (delta SBP 22.6 ± 3.6 mmHg, p<0.0001). At baseline (pre-pregnancy), urinary UMOD levels were 2-fold higher in WKY compared to SHRSP (p<0.05). During pregnancy, the urinary UMOD gradually decreased in WKY (2-fold decrease, p<0.05), whereas a 1.5-fold increase (p<0.05) was observed in hypertensive SHRSP compared to pre-pregnancy. The changes observed in urinary levels corresponded to total kidney UMOD levels at GD18.5, wherein SHRSP kidney shows 1.3-fold (p<0.01) greater expression of UMOD compared to WKY. Nifedipine reduced BP in pregnant SHRSP (delta SBP between GD18.5 and baseline: 44.3 ± 7.4 mmHg, p<0.0001) while propranolol did not affect BP. However, neither nifedipine nor propranolol changed urinary UMOD excretion in pregnant SHRSP. BP was not significantly correlated with urinary uromodulin levels in pregnant WKY (Pearson, r=-0.01, p 0.95) and SHRSP without (r=-0.16, p 0.46) or with (nifedipine r=0.26, p 0.31; propranolol r=0.17, p 0.45) antihypertensive treatment. We demonstrate differences in UMOD excretion between hypertensive and normotensive pregnancy and changes during pregnancy that are at least in part BP independent. Our data provide novel insights into molecular changes associated with hypertensive pregnancy.

The effect of intrauterine growth restriction on Ca2+ -activated force and contractile protein expression in the mesenteric artery of adult (6-month-old) male and female Wistar-Kyoto rats.

Intrauterine growth restriction (IUGR) is known to alter vascular smooth muscle reactivity, but it is currently unknown whether these changes are driven by downstream events that lead to force development, specifically, Ca2+‐regulated activation of the contractile apparatus or a shift in contractile protein content. This study investigated the effects of IUGR on Ca2+‐activated force production, contractile protein expression, and a potential phenotypic switch in the resistance mesenteric artery of both male and female Wistar‐Kyoto (WKY) rats following two different growth restriction models. Pregnant female WKY rats were randomly assigned to either a control (C; N = 9) or food restriction diet (FR; 40% of control; N = 11) at gestational day‐15 or underwent a bilateral uterine vessel ligation surgery restriction (SR; N = 10) or a sham surgery control model (SC; N = 12) on day‐18 of gestation. At 6‐months of age, vascular responsiveness of intact mesenteric arteries was studied, before chemically permeabilization using 50 μmol/L β‐escin to investigate Ca2+‐activated force. Peak responsiveness to a K+‐induced depolarization was decreased (P ≤ 0.05) due to a reduction in maximum Ca2+‐activated force (P ≤ 0.05) in both male growth restricted experimental groups. Vascular responsiveness was unchanged between female experimental groups. Segments of mesenteric artery were analyzed using Western blotting revealed IUGR reduced the relative abundance of important receptor and contractile proteins in male growth restricted rats (P ≤ 0.05), suggesting a potential phenotypic switch, whilst no changes were observed in females. Results from this study suggest that IUGR alters the mesenteric artery reactivity due to a decrease in maximum Ca2+‐activated force, and likely contributed to by a reduction in contractile protein and receptor/channel content in 6‐month‐old male rats, while female WKY rats appear to be protected.

290. Investigation of placental proteome of pregnant stroke-prone spontaneously hypertensive rats

Introduction The stroke-prone spontaneously hypertensive rat (SHRSP) obtained by selective inbreeding of the Wistar-Kyoto (WKY) strain is a well-characterized model of cardiovascular disease. The phenotype of the pregnant SHRSP is reflective of the clinical condition of maternal chronic hypertension during pregnancy. Objective We investigated whether placental proteomics can identify candidate molecules involved in placental dysfunction in pregnant SHRSP. Method Placental proteome of pregnant WKY and SHRSP (n = 5) at gestational day 18 were analyzed using label-free proteomics. Identification and quantitation of protein was performed using LC-MS/MS connected to an LTQ Orbitrap hybrid mass spectroscopy. Functional annotation and gene ontology of proteome was carried out using bioinformatics tools such as DAVID, STRING and Cytoscape. Result Comparison of SHRSP and WKY identified total of 1318 proteins, amongst these 686 were extracellular exosomes proteins, followed by 663 cytoplasm, 486 nucleus and 383 membrane proteins. There were 363 differentially expressed proteins (p value 1.3. Protein interaction networks and gene ontology analysis of these proteins identified major biological process such apoptosis, inflammation, oxidative stress, cell adhesion and migration. We also found 7 and 14 proteins to be uniquely identified only in WKY and SHRSP respectively (p value Discussion The study shows characteristic proteomic pattern in placenta of SHRSP. Further studies into the differentially expressed candidate proteins will give insight into the placental dysfunction in hypertensive pregnancy.

OP.5D.02] TRANSCRIPTOMIC CHANGES IN EARLY PREGNANCY-ASSOCIATED UTERINE ARTERY REMODELLING IN STROKE PRONE SPONTANEOUSLY HYPERTENSIVE RAT

Objective: Deficient spiral artery remodelling is an early gestational defect linked to a number of pregnancy complications such as pre-eclampsia and gestational hypertension. We have previously demonstrated abnormal uterine artery remodelling at gestational day 18 in the stroke prone spontaneously hypertensive (SHRSP) rat. In this study, we examined the early uterine artery structural and functional changes in SHRSP and normotensive Wistar Kyoto (WKY) rats alongside changes in the transcriptome profile. Design and method: Female SHRSP and female WKY rats were time mated at 12 weeks of age ± 4 days. At gestational day 6 (GD6) uterine arteries were dissected and pressure and wire myography performed to assess vascular structure and functional properties. RNAseq (Illumina platform; ribosome depleted, 50 million reads) was performed in uterine arteries from SHRSP and WKY at GD6 and from non-pregnant rats. RNAseq data (FDR < 0.05, FPKM > 1.0) was interpreted using Ingenuity® Pathway Analysis. Results: No significant structural or functional differences were observed in uterine arteries from SHRSP and WKY rats at GD6; cross-sectional area (57.7 ± 1.2 × 103 μm2 vs 67.5 ± 4.2 × 103 μm2), maximal constriction to noradrenaline (41.7 ± 8.1 kPa vs 49.5 ± 9.4 kPa), vasorelaxation to carbachol (76.1 ± 3.9% vs 82.2 ± 3.2%) and SNP (60.5 ± 6.2% vs 58.9 ± 5.8%) (% of maximum constriction) for WKY and SHRSP respectively. RNAseq conducted at GD6, prior to vascular remodelling or functional changes, identified 551 differentially expressed genes between pregnant WKY and pregnant SHRSP; including genes involved in uterine artery vasculogenesis (p-value = 3.78 × 10−10), e.g. angiotensinogen (3.2 fold change, (fc)); angiogenesis (p-value = 3.10 × 10−11), e.g. thrombospondin 4 (4.9 fc); endothelial cell proliferation (p-value = 3.94 × 10−8), e.g. vascular endothelial growth factor D (2.1 fc); and the endothelial nitric oxide synthase pathway (p-value = 3.16 × 10−4), e.g. ryanodine receptor 2 (2.0 fc). Pregnancy resulted in SHRSP-specific increase in expression of NADPH oxidase regulatory subunits p47phox (2.1 fc), p67phox (2.0 fc), p40phox (2.9 fc) p22phox (1.8 fc) and gp91phox (1.8 fc). Conclusions: Uterine artery gene expression during early pregnancy is markedly different between SHRSP and WKY prior to any observed functional and structural changes. Transcriptome profiling implicates pathogenic changes in vasculogenesis and angiogenesis pathways, and endothelial dysfunction, as well as evidence of abnormal oxidative stress response in SHRSP uterine arteries.

Prenatal thyroxine treatment disparately affects peripheral and amygdala thyroid hormone levels

A prenatal hypothyroid state is associated with behavioral abnormalities in adulthood. Wistar Kyoto (WKY) rats exhibit hypothyroidism and increased depressive and anxiety-like behaviors. Thus, the WKY could illuminate the mechanisms by which the reversal of developmental hypothyroidism in humans and animals results in adult behavioral improvement. We examined the outcome of maternal thyroxine (T4) treatment on thyroid hormone-regulated functions and adult behavior of the WKY offspring. Pregnant WKY dams completed gestation with and without T4 administration and their adult male offspring were tested. Measures included depressive and anxiety-like behaviors, and thyroid hormone (TH) concentrations in both plasma and specific brain regions. In addition, the expression of two proteins affecting thyroid hormone trafficking and metabolism, monocarboxylate transporter 8 (MCT-8) and iodothyronine deiodinase type III (Dio3), and of several behavior-altering molecules, glucocorticoid receptor (GR), prepro-thyrotropin releasing hormone (prepro-TRH) and corticotrophin releasing hormone (CRH), were determined in the hippocampus and amygdala of the offspring. Prenatal T4 treatment of WKYs did not affect adult depressive behavior but increased anxiety-like behavior and decreased plasma levels of THs. In the hippocampus of males treated with T4 in utero, Dio3 and MCT-8 protein levels were increased, while in the amygdala, there were increases of free T4, MCT-8, GR, prepro-TRH protein and CRH mRNA levels. These results show that T4 administration in utero programs adult peripheral and amygdalar thyroid hormone levels divergently, and that the resulting upregulation of anxiety-related genes in the amygdala could be responsible for the exacerbated anxiety-like behavior seen in WKYs after prenatal T4 treatment.

Possible involvement of aminopeptidase A in hypertension in spontaneously hypertensive rats (SHRs) and change of refractoriness in response to angiotensin II in pregnant SHRs.

Hypertension complicated with pregnancy is a major cause of maternal and fetal mortality, but its pathophysiology is unclear. To investigate the pressor response to angiotensin II (Ang II) and the involvement of the Ang II degrading protease, aminopeptidase A, in spontaneously hypertensive rats (SHRs). Pregnant SHRs and Wistar-Kyoto (WKY) rats were studied. Angiotensin II (200 ng/kg per min) or saline was infused by osmotic pump from day of 15 gestation, and caesarean section was performed at day 20 of gestation. Blood pressure during pregnancy, weight of placentas and pups at caesarean section, and aminopeptidase A activity in placenta and renal cortex were measured. Ang II treatment induced increases in blood pressure that were greater in non-pregnant WKY rats than those in pregnant WKY rats, pregnant SHRs, and non-pregnant SHRs. Renal aminopeptidase A activity in SHRs was significantly lower than that in WKY rats. Renal aminopeptidase A activity in pregnant SHRs was significantly greater than that in non-pregnant SHRs, but there was no significant increase in pregnant WKY rats. Placental aminopeptidase A activity in SHRs was greater than that in WKY rats. Placental aminopeptidase A activity in WKY rats was increased by Ang II, but was not increased in SHRs. Weights of placentas and pups were significantly lower in SHRs than in WKY rats. Renal aminopeptidase A may be involved in the development of hypertension and the regulation of blood pressure in SHRs. Placental aminopeptidase A may be upregulated in response to fetal stress in pregnant SHRs.

Effects of hypertension on maternal adaptations to pregnancy: experimental study on spontaneously hypertensive rats.

Animal models for essential hypertension have been used for understanding the human pathological conditions observed in pregnant hypertensive women. To study the possible effects of pregnancy on hypertension and of hypertension on pregnancy in spontaneously hypertensive rats (SHR), and in their normotensive Wistar-Kyoto (WKY) counterparts. Comparative study using laboratory animals. Animal Research Laboratory of Clinical Medicine at the Medical School of Botucatu, São Paulo State University, Brazil. Ten to twelve-week-old virgin female normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The animals were separated into four groups: 15 pregnant spontaneously hypertensive rats (SHR-P), 10 non-pregnant spontaneously hypertensive rats (SHR-NP), 15 pregnant normotensive rats (WKY-P), and 10 non-pregnant normotensive rats (WKY-NP). The blood pressure was evaluated by the tail cuff method, in rats either with or without prior training for the handling necessary for tail cuff measurements. The maternal volume expansion was indirectly evaluated by weight gain, and by systemic parameters as hematocrit, hemoglobin, total protein, albumin and sodium retention. The perinatal outcome of pregnancy was evaluated by analysis of resorptions, litter size, rate of low weight and number of stillbirths. The late fall in blood pressure in the pregnant SHR strain and in the normotensive WKY strain can only be detected in rats previously trained to accept the handling necessary for the tail cuff measurement. During pregnancy the body weight gain was significantly higher in WKY than in SHR rats. Systemic parameters were significantly lower in pregnant WKY rats than in non-pregnant WKY rats, while no differences were observed between pregnant and non-pregnant SHR groups. In pregnant WKY rats the sodium retention was higher from the 13th day onwards, while in SHR rats this occurred only on the 21st day. The characteristics of reproductive function such as number and weight of fetus, perinatal mortality and the resorption rate were significantly affected in the SHR strain. The SHR strain may be considered as a model for chronic hypovolemic maternal hypertension, with the fetal growth retardation being determined by this hypovolemic state.

Corticosteroid dynamics in the nonpregnant, pregnant, and postpartum spontaneously hypertensive rat

Factors responsible for hypertension in the spontaneously hypertensive rat (SHR) remain under investigation. As in human pregnancy complicated by essential chronic hypertension, the hypertension of the pregnant SHR subsides and returns postpartum. Because corticosteroid excess can cause hypertension, we examined several aspects of adrenocortical activity as potentially affecting the reported blood pressure profiles of nonpregnant, term pregnant, and postpartum SHR, using normotensive Wistar-Kyoto (WKY) rats as controls. We found that corticosterone levels were comparable in nonpregnant SHR and WKY rats, and unaffected by pregnancy. No differences were detected postpartum. Although pregnancy was accompanied by significant increases in plasma aldosterone levels, no interbreed differences were observed, which remained the case postpartum. Single adrenal cell secretion of aldosterone and corticosterone, as detected by reverse hemolytic plaque assay, yielded similar results in the pregnant and postpartum rat. Hormone responses to dietary manipulations in the nonpregnant and pregnant SHR and WKY suggest an important role for ACTH, and a lesser one for AII in the regulation of corticosteroids. In situ hybridization histochemistry, using a probe that detects both P450c11β and P450c11AS mRNA, revealed comparable message density and zonal distribution in adrenals from pregnant and nonpregnant SHR and WKY rats. Breed- and pregnancy-dependent differences in adrenal expression of P450scc, P450c11β, and P450c11AS were noted. In summary, our findings suggest that although some discrepancies exist in the aspects of adrenocortical activity examined, they are unlikely to be etiologic in the blood pressure profile observed in nonpregnant, pregnant, and postpartum SHR.

Neuropeptide Y and mesenteric sympathetic vasoconstriction in pregnant and non-pregnant Wistar-Kyoto rats.

1. We have investigated the role of neuropeptide Y (NPY) in sympathetic vasoconstriction and its possible contribution to decreased mesenteric vasoconstrictor responses to electrical field stimulation (EFS) in pregnancy in vivo using an in situ bloodperfused mesenteric preparation in 18-20 day pregnant and age-matched non-pregnant Wistar-Kyoto (WKY) rats. 2. Mean blood pressure (BP) was decreased in pregnant compared with non-pregnant rats. Mesenteric basal perfusion pressure (PP) was not significantly reduced in pregnancy. BIBP 3226, a specific NPY Y1 receptor antagonist, did not affect mean BP or mesenteric basal PP in pregnant or non-pregnant animals. 3. Mesenteric vasoconstrictor responses to EFS were blunted in pregnant compared with non-pregnant controls. BIBP 3226 significantly suppressed mesenteric vasoconstrictor responses to EFS in both pregnant and non-pregnant animals. Decreased mesenteric responses to EFS in pregnancy were still evident following NPY Y1 receptor blockade. 4. These results suggest that endogenous NPY plays a role in rat mesenteric sympathetic vasoconstriction in vivo. However, NPY is unlikely to be responsible for the impairment of EFS-induced mesenteric vasoconstriction in pregnant WKY rats.

The role of angiotensin converting enzyme and nitric oxide in the enhanced systemic depressor responses to bradykinin in pregnant rats.

1. In the present study we have examined the effects of angiotensin I converting enzyme (ACE) inhibition and nitric oxide (NO) synthesis inhibition on bradykinin (BK) depressor responses in pregnancy in both Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Ramipril (10 mg/kg, i.v.) significantly reduced mean blood pressure (MBP) in all animals. Further administration of L-nitro-arginine (L-NOARG, 20 mg/kg, i.v.) increased MBP to a less extent in pregnant WKY and to a similar level in pregnant SHR compared with their non-pregnant controls (controls), respectively. 3. Systemic depressor responses to BK were increased in pregnant WKY and were unchanged in pregnant SHR as compared with their controls. Ramipril (10 mg/kg, i.v.) potentiated BK responses in all groups, and abolished the differences between pregnant and non-pregnant WKY. Further administration of L-NOARG (20 mg/kg, i.v.) did not further influence BK responses in all groups. 4. The results suggest that systemic depressor responses to BK are enhanced in pregnant WKY and unchanged in pregnant SHR. Decreased ACE activity may contribute to enhanced systemic depressor responses to BK in pregnant WKY.

Nitric oxide‐mediated changes in vascular reactivity in pregnancy in spontaneously hypertensive rats

1. To examine the mechanisms which may account for pregnancy-induced vasodilatation in spontaneously hypertensive rats (SHR), we have investigated the changes in vascular reactivity and the effects of endothelial nitric oxide (NO) inhibition in the in situ blood-perfused, mesenteric resistance vessels of 18-20 day pregnant SHR. The effects of NG-nitro-L-arginine (L-NOARG) were compared in pregnant and nonpregnant SHR and gestation matched normotensive Wistar-Kyoto (WKY) rats. 2. Intra-arterial mean blood pressures (MBP) were similar in pregnant and nonpregnant SHR. Basal perfusion pressures (BPP) were decreased in pregnant compared with nonpregnant SHR. Pregnant WKY had lower MBP and BPP than either pregnant or nonpregnant SHR. 3. Vasoconstrictor responses to electrical stimulation (ES) and intra-arterial noradrenaline (NA) were decreased in pregnant compared with nonpregnant SHR. These responses were still greater in pregnant SHR when compared with pregnant WKY. Vascular reactivity to angiotensin II (AII) in pregnant SHR was reduced to a similar level to that in pregnant WKY. 4. L-NOARG (5 mg kg-1, i.v.), an inhibitor of nitric oxide synthase, increased MBP and BPP in all groups. After L-NOARG, BPP were equalized between pregnant and nonpregnant SHR. Pregnant WKY still showed lower MBP and BPP than SHR groups. 5. L-NOARG potentiated vascular responses to ES, NA and AII in all groups. The blunted vascular responses to NA and ES were normalized and the reactivity to AII was only partially reversed in pregnant SHR compared with nonpregnant SHR. Pregnant WKY still had much lower vascular responses to ES and NA than either pregnant or nonpregnant SHR. L-NOARG enhanced vascular responses to All to a greater extent in pregnant SHR than in pregnant WKY.6. These results demonstrate that blunted responses to NA and ES were NO-dependent, while diminished reactivity to AII was only partially dependent on NO in the in situ blood perfused mesenteric resistance vessels of pregnant SHR.7. The present results in pregnant SHR differ from our previous finding with pregnant normotensive WKY, in which blunted responses to NA, but not to ES, were equalized by L-NOARG. Pregnancy induced vasodilatation in hypertensive rats appears to be more dependent on endothelial NO than in normotensive WKY. A defect of the endothelial NO generating pathway which promotes vasodilatation in pregnancy may contribute to the predisposition of women with essential hypertension to develop pre-eclampsia.

Kidney function and sodium handling in the pregnant spontaneously hypertensive rat.

Effects of gestation on volume homeostasis and renal function were studied in awake spontaneously hypertensive rats (SHR). Systolic blood pressure was similar to that of virgin littermates during most of SHR pregnancy but decreased near term (p less than 0.005). Plasma renin activity was lower in SHR than in age-matched Wistar-Kyoto (WKY) rats (p less than 0.001), but values were similar in gravid and nonpregnant animals from each strain. Renal renin content and lipid volume fractions of papillary interstitial granules were significantly greater in pregnant animal of each strain and those of the gravid WKY were also greater than both pregnant and virgin SHR. Saralasin had no effect on mean arterial pressure in gravid and virgin rats from either group. Plasma volume increased significantly near term in animals of both strains. Kidney weight, glomerular filtration rate (GFR), and renal blood flow were lower in SHR compared to WKY, and the hypertensive rats failed to demonstrate an increase in GFR during gestation, unlike the WKY. All SHR and pregnant WKY excreted infused sodium better than the virgin WKY. Also, regular Wistar animals excreted a salt load better than the virgin WKY. Finally, uterine blood flow, pup number and conceptus weight were similar in SHR and WKY. We conclude that pregnancy induces a decrease in blood pressure in SHR, and that angiotensin II does not seem to play an important role in maintaining blood pressure during gestation in either SHR or WKY. Despite a lower GFR and its failure to increase during pregnancy, renal sodium handling is not impaired in the SHR. The virgin WKY has a decreased ability to excrete sodium which is ameliorated during gestation.