Blood Pressure In Pregnant Rats Research Articles

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor†.

Obstructive sleep apnea is a recognized risk factor for gestational hypertension, yet the exact mechanism behind this association remains unclear. Here, we tested the hypothesis that intermittent hypoxia, a hallmark of obstructive sleep apnea, induces gestational hypertension through perturbed endothelin-1 signaling. Pregnant Sprague-Dawley rats were subjected to normoxia (control), mild intermittent hypoxia (10.5% O2), or severe intermittent hypoxia (6.5% O2) from gestational days 10-21. Blood pressure was monitored. Plasma was collected and mesenteric arteries were isolated for myograph and protein analyses. The mild and severe intermittent hypoxia groups demonstrated elevated blood pressure, reduced plasma nitrate/nitrite, and unchanged endothelin-1 levels compared to the control group. Western blot analysis revealed decreased expression of endothelin type B receptor and phosphorylated endothelial nitric oxide synthase, while the levels of endothelin type A receptor and total endothelial nitric oxide synthase remained unchanged following intermittent hypoxia exposure. The contractile responses to potassium chloride, phenylephrine, and endothelin-1 were unaffected in endothelium-denuded arteries from mild and severe intermittent hypoxia rats. However, mild and severe intermittent hypoxia rats exhibited impaired endothelium-dependent vasorelaxation responses to endothelin type B receptor agonist IRL-1620 and acetylcholine compared to controls. Endothelium denudation abolished IRL-1620-induced vasorelaxation, supporting the involvement of endothelium in endothelin type B receptor-mediated relaxation. Treatment with IRL-1620 during intermittent hypoxia exposure significantly attenuated intermittent hypoxia-induced hypertension in pregnant rats. This was associated with elevated circulating nitrate/nitrite levels, enhanced endothelin type B receptor expression, increased endothelial nitric oxide synthase activation, and improved vasodilation responses. Our data suggested that intermittent hypoxia exposure during gestation increases blood pressure in pregnant rats by suppressing endothelin type B receptor-mediated signaling, providing a molecular mechanism linking intermittent hypoxia and gestational hypertension.

The Role of High Calcium Diet Supplementation on L-NAME induced High Blood Pressure in Pregnant Rats

Background: Hypertension in pregnancy with or without proteinuria is one of the foremost reasons of maternal death and morbidity in the world. This study investigated the role of a high calcium diet (HCa) in N G -nitro-L-arginine methyl ester (L-NAME) administered to pregnant rats. Methods: Thirty-two female rats of the Sprague-Dawley strain were randomly assigned into 4 groups of control, L-NAME (0.3g/ L of water), L-NAME + HCa (2.5%), and HCa diet (2.5%) group. Following confirmation of mating, HCa was administered from day 3 to day 18 of pregnancy while L-NAME was administered from day 12 to 18. The rats were sacrificed on the 19th day and blood pressure measurements were obtained. Blood and placenta were collected for biochemical and oxidative assays. Results: Blood pressure was reduced in L-NAME + HCa rats compared with L-NAME (p<0.05). Placenta and fetal weight were decreased in rats receiving L-NAME, L-NAME + HCa and HCa compared with control (p<0.05). HCa diet had no effect on L-NAME impaired oxidative status. No significant difference was observed in the liver enzymes and CRP levels across the groups. However, there was a significant reduction in the platelet count of L-NAME + HCa and HCa groups when compared with the control and L-NAME. Calcium and magnesium levels in the serum and placenta homogenate were not different but their excretion was significantly increased in the urine samples of the L-NAME + HCa and HCa groups. Conclusion: This study showed that HCa reduced the blood pressure of pregnant rats administered L-NAME but had no effect on oxidative stress. This implies that HCa alone might not sufficiently ameliorate the negative effects of hypertension in pregnancy.

In vivo study of the antihypertensive effect of bidara leaf (Ziziphus spina-christi) during pregnancy

Background: Bidara is drought tolerant and very easy to grow in tropical climates such as Indonesia. Bidara contains a combination of calcium, potassium, and magnesium, and active flavonoid compounds, and antioxidant activity that play a role in inhibiting free radical damage, improving endothelial function so that it can potentially lower blood pressure. Previous studies explained that a dose variant of no more than 300mg/kg BW is beneficial while minimizing pathological changes. However, there has been no research related to the effect of bidara leaf in lowering blood pressure, so it is necessary to do related research.Objective: Analyze the effect of bidara leaf extract at a 200 mg/kg BW dose and 300 mg/kg BW on systolic and diastolic blood pressure.Methods: 24 pregnant female Wistar rats induced hypertension, aged 6-8 weeks with a weight of 130-230 grams. The rats were randomized so that they consisted of 2 control groups and two experimental groups, which were given various doses of bidara leaf for nine days. Blood pressure was measured using non-invasive CODA.Results: The blood pressure of rats in the bidara leaf extract group at doses of 200mg/kg BW and 300mg/kg BW decreased systolic and diastolic compared to the control group (p<0.05). The 200mg/kg BW dose group experienced a decrease in blood pressure of 12.3% for systolic and 16.32% for diastolic; the 300mg/kg BW dose group experienced a decrease in blood pressure of 19.99% for systolic and 27.73% for diastolic.Conclusion: Bidara leaf extract can reduce the blood pressure of pregnant rats with hypertension.

Cardiac and Hepatic miRNAs Altered Expression in Rat Embryo after Bisphenol-A (BPA) Exposure and Their Histopathological Impact (In vivo Study)

Introduction: Plastic compound are widely used in modern life. Bisphenol-A is an essential component in high quality plastic containers such as bottles and food boxes. Beside its hormonal agonist and antagonist effects, Food and drug administration (FDA) had reported it is transmitted from mother to fetus through placental circulation causing mi-RNAs mutation. mi-RNAs regulate cellular morphology and functions through its essential role in genetic expression. The aim of the present study is to investigate the effect of exposure of BPA on maternal [placenta, body weight & blood pressure] and fetal [liver, heart & miRNAs expression] and the impact of miRNAs expression disorders on multiorgan development, namely cardiac and hepatic development.
 Materials and Methods: 60 healthy pregnant females’ rats were picked up since day one of gestation and divided into three groups (n=20). (c) control group gained access to drinking water containing only the vehicle (tween-80) 0.1/ml for three weeks.(10-BPA) group, gained access to drinking water containing 10 mg/L of BPA for three weeks.(20-BPA) group, gained access to drinking water containing 20 mg/L of BPA for three weeks. Placenta, liver and heart samples were collected and histopathological changes were recorded and mi-RNAs expression was investigated.
 Results: Histopathological changes were noticed in BPA related groups if compared to control group. mi-RNAs expression was found in same groups with variable extent. A significant increase was noticed in body weight and blood pressure of pregnant rats.
 Conclusion: Our data examined the impact of BPA exposure on different organs and their related miRNAs expression which showed a non-neglectable effect especially on the placenta of the mother and fetal heart and liver.

Hypoxia-induced small extracellular vesicle proteins regulate proinflammatory cytokines and systemic blood pressure in pregnant rats.

Small extracellular vesicles (sEVs) released from the extravillous trophoblast (EVT) are known to regulate uterine spiral artery remodeling during early pregnancy. The bioactivity and release of these sEVs differ under differing oxygen tensions and in aberrant pregnancy conditions. Whether the placental cell-derived sEVs released from the hypoxic placenta contribute to the pathophysiology of preeclampsia is not known. We hypothesize that, in response to low oxygen tension, the EVT packages a specific set of proteins in sEVs and that these released sEVs interact with endothelial cells to induce inflammation and increase maternal systemic blood pressure. Using a quantitative MS/MS approach, we identified 507 differentially abundant proteins within sEVs isolated from HTR-8/SVneo cells (a commonly used EVT model) cultured at 1% (hypoxia) compared with 8% (normoxia) oxygen. Among these differentially abundant proteins, 206 were up-regulated and 301 were down-regulated (P < 0.05), and they were mainly implicated in inflammation-related pathways. In vitro incubation of hypoxic sEVs with endothelial cells, significantly increased (P < 0.05) the release of GM-CSF, IL-6, IL-8, and VEGF, when compared with control (i.e. cells without sEVs) and normoxic sEVs. In vivo injection of hypoxic sEVs into pregnant rats significantly increased (P < 0.05) mean arterial pressure with increases in systolic and diastolic blood pressures. We propose that oxygen tension regulates the release and bioactivity of sEVs from EVT and that these sEVs regulate inflammation and maternal systemic blood pressure. This novel oxygen-responsive, sEVs signaling pathway, therefore, may contribute to the physiopathology of preeclampsia.

AT1R antagonism improves metabolic and vascular changes of obesity-induced gestational diabetes mellitus

Obesity can overload glucose homeostasis and physiological insulin resistance during gestation which increases the risk of complications like diabetes mellitus or preeclampsia. Angiotensin II /AT1 receptors are involved in the pathogenesis of vascular effects of obesity/insulin resistance but its role during gestation is not as clear. We sought to determine angiotensin II- AT1R participation on a diet-induced gestational diabetes mellitus (GDM) experimental model. Female Wistar rats were fed with a standard or hypercaloric diet for 7 weeks. Half of the animals were mated and became pregnant from week 4–7. Animals were treated with saline, irbesartan (30 mg/kg) or metformin (320 mg/kg) for the last two weeks of the protocol. Weight gain, systolic blood pressure (BP), oral glucose tolerance test and vascular contractility were measured at the last day of the protocol (day 19–20 of pregnancy). Hypercaloric diet increased blood glucose, impaired glucose tolerance test, and increased BP in pregnant rats, fulfilling criteria for GDM. Both drugs decreased impaired GTT and relative hyperglycemia. Metformin had no effect on BP but prevented weight increase. In isolated aortas, irbesartan and metformin decreased vasoconstriction only of non-pregnant hypercaloric diet fed animals.Results support angiotensin II/ AT1R involvement in BP and glucose homeostasis disturbances observed in present GDM model. Also, provide evidence that a hypercaloric diet can mask pregnancy´s physiological hypoglycemia and hypotension without surpassing non-pregnant values. Then, we conclude overweight during pregnancy causes subtle but significant vascular and metabolic damage that might be dismissed in clinical practice.

Placental protein 13 (PP13) stimulates rat uterine vessels after slow subcutaneous administration.

IntroductionReduced concentrations of placental protein 13 (PP13) during the first trimester of human pregnancy are associated with elevated risk for the subsequent development of preeclampsia, which is one of the deadliest obstetrical complications of pregnancy. Previous studies by our group have shown that PP13 lowers blood pressure in pregnant rats, increases the size and weight of pups and placentas, and induces vasodilation of resistance arteries through endothelial signaling pathways involving endothelial nitric oxid synthase and prostaglandin.MethodsIn the present study, the effect of PP13 was investigated in nonpregnant female Sprague Dawley rats (n=27). Osmotic pumps were surgically implanted subcutaneously that released a constant dose of PP13 or saline over 7 days. Most animals were sacrificed 6 days after the end of PP13 release (on day 13), while some were sacrificed immediately at the end of day 7 (the last PP13 release day), to compare the short- and long-term impact of PP13 on vessels’ growth and size.ResultsThe uterine vessels were significantly expanded in the group exposed to recombinant PP13 (rPP13) compared to the control (saline) group. Both veins and arteries were significantly expanded by rPP13 with a more pronounced effect after 13 days compared to the corresponding vessels after 7 days. Furthermore, the long-term effect of treatment by rPP13 was more pronounced in the veins compared to the corresponding arteries. The effect of a PP13 variant with a histidine-tag (His-PP13) remained the same between 7 and 13 days.ConclusionIn conclusion, PP13 might play a key role in the expansive remodeling of the uterine vessels, reflecting what would happen if the rat was pregnant, preparing the uterine vascu-lature for the increase in uteroplacental blood flow, which is necessary for normal pregnancy. We suggest that PP13 could act by NO signaling pathways, a hypothesis that requires future study.

Oxidative Stress in the Rostral Ventrolateral Medulla Contributes To Cardiovascular Regulation in Preeclampsia.

Background: It has been demonstrated that preeclampsia, a pregnancy-specific hypertension disorder, is characterized by high blood pressure (BP) and sympathetic overactivity. Increased reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM), a key region for controlling sympathetic tone, has been reported to contribute to high level of BP and sympathetic outflow. The aim of the present study was to determine the role of the RVLM ROS in mediating the preeclampsia-associated cardiovascular dysfunction.Methods: The animal model of preeclampsia was produced by administration of desoxycorticosterone acetate (DOCA) to pregnant rats.Results: Compared with normal pregnant rats without DOCA treatment (NP), the protein concentration and norepinephrine excretion in 24-h urine, as well as BP in pregnant rats with DOCA treatment (PDS) were significantly increased. The levels of superoxide anion and the protein expression of NADPH oxidase subtype (NOX4) in the RVLM were significantly increased in PDS than in NP groups. Furthermore, microinjection of the superoxide dismutase (SOD) mimic Tempol (5 nmol) into the RVLM significantly decreased BP, heart rate, and renal sympathetic never activity in PDS but not in NP group.Conclusion: The present data suggest that high BP and sympathetic overactivity in preeclampsia rats is associated with increased oxidative stress in the RVLM via upregulation of NOX4 expression.

Single administration of ultra-low-dose lipopolysaccharide in rat early pregnancy induces TLR4 activation in the placenta contributing to preeclampsia.

Balanced immune responses are essential for the maintenance of successful pregnancy. Aberrant responses of immune system during pregnancy increase the risk of preeclampsia. Toll-like receptor 4 (TLR4) plays a crucial role in the activation of immune system at the maternal-fetal interface. This study aimed to generate a rat model of preeclampsia by lipopolysaccharide (LPS, a TLR4 agonist) administration on gestational day (GD) 5 as rats are subjected to placentation immediately after implantation between GDs 4 and 5, and to assess the contribution of TLR4 signaling to the development of preeclampsia. Single administration of 0.5 μg/kg LPS significantly increased blood pressure of pregnant rats since GD 6 (systolic blood pressure, 124.89 ± 1.79 mmHg versus 119.02 ± 1.80 mmHg, P < 0.05) and urinary protein level since GD 9 (2.02 ± 0.29 mg versus 1.11 ± 0.18 mg, P < 0.01), but barely affected blood pressure or proteinuria of virgin rats compared with those of saline-treated pregnant rats. This was accompanied with adverse pregnancy outcomes including fetal growth restriction. The expression of TLR4 and NF-κB p65 were both increased in the placenta but not the kidney from LPS-treated pregnant rats, with deficient trophoblast invasion and spiral artery remodeling. Furthermore, the levels of inflammatory cytokines were elevated systemically and locally in the placenta from pregnant rats treated with LPS. TLR4 signaling in the placenta was activated, to which that in the placenta of humans with preeclampsia changed similarly. In conclusion, LPS administration to pregnant rats in early pregnancy could elicit TLR4-mediated immune response at the maternal-fetal interface contributing to poor early placentation that may culminate in the preeclampsia-like syndrome.

Transplantation of endothelial progenitor cells for improving placental perfusion in preeclamptic rats.

Effective treatments for preeclampsia are currently unavailable. As endothelial progenitor cell-transplantation may improve ischemia, it is an important undertaking to study the role of endothelial progenitor cells for improving the symptom of preeclampsia. Physiological and pathological changes in foetal rats and pregnant rats were monitored. Endothelial progenitor cells were isolated from the peripheral blood of normal rats and labelled by DiI. Endothelial progenitor cells were transplanted into the placenta of preeclampsia-like rats. Fluorescence microscopy was used to observe the differentiation of transplanted endothelial progenitor cells. Western blotting was used to observe the expression of nestin, an index of brain hypoxia in foetal rats. The rats suffered from abdominal aortic constriction and NG-nitro-L-arginine methyl ester injection (group F). The proteinuria and blood pressure of pregnant rats in group F increased on the 13th day of pregnancy. The proteinuria and blood pressure of group F was higher than in other groups of rats. The weight of foetal rats and foetal heads significantly decreased in group F compared with other groups. Typical pathological changes of preeclampsia were observed in the placental tissue of group F. In preeclampsia-like rats, transplantation of endothelial progenitor cells led to an increase in placenta angiogenesis. The expression of nestin weakened in endothelial progenitor cell-transplanted rats compared with the non-transplantation group. After EPCs transplantation, physiological parameters in the preeclampsia-like rats were significantly decreased. Endothelial progenitor cells transplantation could improve preeclampsia-like symptom in rats and endothelial progenitor cell-transplantation relieves intrauterine hypoxia in brain tissues of foetal rats to a certain extent.

644: Effects of reduced uterine perfusion pressure on postpartum blood pressure in pregnant rats

644: Effects of reduced uterine perfusion pressure on postpartum blood pressure in pregnant rats

PLACENTAL HEME OXYGENASE ACTIVITY REDUCTION IS ASSOCIATED WITH HYPERTENSION IN PREGNANT RATS

Reduction in the placental perfusion pressure has long been thought to underlie preeclampsia (PE). It has also been demonstrated that inhibition of heme oxygenase (HO) activity in isolated placenta increases placental perfusion pressure. This finding suggests that the HO‐CO system is involved in regulating blood flow to this organ. However, it is unknown whether the reduction of placental HO activity produces hypertension during gestation, which is a common feature in PE. Therefore, the aim of this study was to determine whether administration of an HO inhibitor during gestation induces an elevation in blood pressure (BP) and whether the hypertension is associated to a reduced placental HO activity. The HO inhibitor, stannous mesoporphyrin (SnMP; 50 micromol/kg i.p) or vehicle (sodium carbonate) were administered to virgin (n=6) and pregnant rats (n=7) at day 14 of gestation. BP was measured 5 days later in conscious rats. SnMP increased (p&lt;0.01) BP in pregnant rats (114 ± 1 vs 100 ± 2 mmHg) but had no effect in virgin rats (121 ± 2 vs 124 ± 3 mmHg). This increase was associated to a reduction in placental HO activity (10.4 ± 0.5 vs 6.9 ± 0.2 ng/bilirubin/μg protein/h, p&lt;0.05) and an important fetal reabsorption (4.0 ± 0.7 vs 1.0 ± 0.3, p&lt;0.05), indicating possible placental ischemia. These results suggest that the HO‐CO system may play an important role in the development of PE.

Renal 20-HETE inhibition attenuates changes in renal hemodynamics induced byl-NAME treatment in pregnant rats

We previously reported that inhibition of nitric oxide (NO) synthesis by N-nitro-L-arginine methyl ester (L-NAME) during late pregnancy leads to increased production of renal vascular 20-hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P-450 (CYP) 4A-derived vasoconstrictor, in pregnant rats. However, the effect of upregulation of vascular 20-HETE production on renal function after NO inhibition is not known. To test the hypothesis that increased gestational vascular 20-HETE synthesis after NO inhibition is involved in mediating blood pressure and renal functional changes, we first determined the IC(50) value of the effect of nitroprusside (SNP), a NO donor, on renal 20-HETE production in cortical microsomes. We then divided pregnant rats and age-matched virgin rats into a vehicle control group, an L-NAME treatment group (0.25 mg/ml in drinking water), and a group treated with L-NAME plus N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS; CYP4A-selective inhibitor, 10 mg.kg(-1).day(-1) iv). After 4 days of treatment, we measured blood pressure, renal blood flow (RBF), renal vascular resistance (RVR), and glomerular filtration rate (GFR) in each group. The addition of SNP (IC(50) = 22 microM) decreased renal cortical 20-HETE production. In pregnant rats, L-NAME treatment led to significantly higher mean arterial pressure (MAP) and RVR, and lower RBF and GFR. Combined treatment with DDMS and L-NAME significantly attenuated the increases in MAP and RVR and the decrease in GFR, but not the reduction in RBF induced by L-NAME treatment. L-NAME and L-NAME plus DDMS had no significant impact on renal hemodynamics in virgin rats. In addition, chronic treatment with DDMS selectively inhibited cortical 20-HETE production without a significant effect on CYP4A expression in L-NAME-treated pregnant rats. In conclusion, NO effectively inhibits renal cortical microsomal 20-HETE production in female rats. In pregnant rats, the augmentation of renal 20-HETE production after NO inhibition is associated with increased MAP and RVR, whereas decreased GFR is negated by treatment of a selective and competitive CYP4A inhibitor. These results demonstrate that the interaction between renal 20-HETE and NO is important in the regulation of renal function and blood pressure in pregnant rats.

Antibody to marinobufagenin lowers blood pressure in pregnant rats on a high NaCl intake

The pathogenesis of pre-eclampsia (PE), a major cause of maternal and fetal mortality, is not fully understood. Digitalis-like sodium pump ligands (SPLs) are believed to be implicated in PE, as illustrated by clinical observations that DIGIBIND, a digoxin antibody that binds SPLs, lowers blood pressure (BP) in PE. We recently reported that plasma levels of marinobufagenin (MBG), a vasoconstrictor SPL, are increased four-fold in patients with PE. In the present study, we tested whether a polyclonal antibody to MBG can lower BP in rats with pregnancy-associated hypertension. Systolic BP (SBP), 24-h renal excretion of MBG and endogenous ouabain (EO), and sodium pump activity in the thoracic aortae were measured in virgin and pregnant Sprague-Dawley rats without and with NaCl supplementation (drinking 1.8% NaCl solution). NaCl supplementation of virgin rats stimulated renal excretion of MBG by 60%, but not that of EO, and did not change the BP. Compared with virgin rats, the last week of pregnancy in non-NaCl-loaded rats was associated with a decrease in SBP (106 +/- 2 versus 117 +/- 2 mmHg); a moderate increase in renal excretion of MBG (97.6 +/- 4.9 versus 57.4 +/- 7.0 pmoles/24 h) and EO (36.2 +/- 4.3 versus 24.1 +/- 3.2 pmoles/24 h). NaCl-loaded pregnant rats exhibited elevation in SBP (139 +/- 3 mmHg; P < 0.01 versus non-NaCl-loaded pregnant rats), in renal excretion of MBG (160.0 +/- 17.5 pmoles/24 h; P < 0.01 versus non-NaCl-loaded pregnant rats), but not in EO, and showed fetal growth retardation. Administration of the anti-MBG antibody to NaCl-loaded pregnant rats lowered SBP (111 +/- 2 mmHg; P < 0.01) and increased aortic sodium pump activity (144 +/- 3 versus 113 +/- 5 nmol Rb/g per min; P < 0.01 versus non-NaCl-loaded pregnant rats). These observations provide evidence that MBG contributes to BP elevation in pregnant rats rendered hypertensive by NaCl supplementation.

High sodium intake stimulates endogenous sodium pump inhibitor, marinobufagenin, and increases blood pressure in pregnant rats

Previous studies have implicated endogenous digitalis-like sodium pump ligands in pathogenesis of preeclampsia. Recently, we have shown that an endogenous bufadienolide, marinobufagenin (MBG), an inhibitor of ouabain resistant alpha-1 Na/K-ATPase, rather than endogenous ouabain (EO) becomes elevated and contributes to hypertension in patients with preeclampsia (Lopatin et al, J Hypertens 1999; 17: 1179-87) and in Dahl-S rats on a high NaCl intake (Fedorova et al, Circulation 2002; 105: 1122-27). We hypothesized that in pregnant rats on a high NaCl intake MBG increases and contributes to blood pressure (BP) elevation. Renal excretion of MBG, EO and sodium, systolic BP, and plasma renin activity (PRA) were compared in non-pregnant and pregnant Sprague-Dawley rats (225-250 g) during last week of pregnancy. Pregnant animal consumed either water or NaCl solution, 0.9% or 1.8%. As compared with non-pregnant rats, last week of pregnancy was associated with decreased systolic BP, increased PRA and moderate increases in renal excretion of MBG and EO. NaCl supplementation induced graded increases in renal Na excretion, in systolic BP and renal excretion of MBG and with concomitant decrease in PRA (Table). Supplementation with 1.8% NaCl was also associated with fetal growth retardation. Our results demonstrate that in rats NaCl supplementation during the last week of pregnancy induces preeclampsia-like symptoms including elevation of BP, proteinuria, suppression of PRA and fetal growth retardation. Elevations of BP are associated with enhanced excretion of MBG, which makes MBG a potential target for therapy. One-way ANOVA followed by Newman-Keuls test. -P<0.05, -P<0.01 vs. nonpregnant rats; -P<0.05, -P<0.01 vs. pregnant rats without NaCl supplementation. n=12–15 for each group. One-way ANOVA followed by Newman-Keuls test. -P<0.05, -P<0.01 vs. nonpregnant rats; -P<0.05, -P<0.01 vs. pregnant rats without NaCl supplementation. n=12–15 for each group.

Calcium channels contribute to the decrease in blood pressure of pregnant rats.

Pregnancy is associated with hemodynamic changes such as reduced vascular resistance and blood pressure. We reported that, during late pregnancy, the activity of voltage-dependent calcium channels (VDCC) is altered in the adrenal cortex and vascular smooth muscle. These observations suggested that the late pregnancy-induced decrease in blood pressure is linked to diminished VDCC function. We attempted to prevent pregnancy-induced reduced blood pressure with a calcium channel activator (CGP 28392) in pregnant rats and to mimic it by administration of a calcium channel blocker (nifedipine) to nonpregnant rats. Treatment was given from the 15th day of gestation for 7 days. The systolic blood pressure of CGP 28392-treated pregnant rats rose transiently for 2 days and then declined toward values of nontreated pregnant controls, although remaining higher. However, nonpregnant rats maintained their high arterial pressure throughout CGP 28392 treatment. Nifedipine lowered the blood pressure in nonpregnant rats to values of nontreated term-pregnant controls. Both agents did not affect body weight, water or food intake, plasma renin activity, and plasma aldosterone or corticosterone levels. Nifedipine and CGP 28392 treatment of nonpregnant and pregnant animals, respectively, did not modify the response of aortic rings to KCl. These results show that VDCC activation caused hypertension, which modified the extent of the decrease in blood pressure at the end of pregnancy.

Blood Pressure Effects of Angiotensin II and Vasopressin in Conscious Pregnant Normotensive and Spontaneously Hypertensive Rats

In order to determine vascular reactivity to vasoconstrictor agents during pregnancy in hypertensive animals, dose-response curves to the pressor effect of angiotensin II (AII) and arginine8-vasopressin (AVP) were measured in unrestrained, conscious and catheterized normotensive, Sprague-Dawley (SD), Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats at the end of pregnancy and in non-pregnant animals. At the end of gestation, the sensitivity to both agents was decreased by a factor varying from 1.3 to 2.1 in the three strains of rats. The blood pressure reached by each dose of AII and AVP was lower during gestation in the three strains. This was not the result of lower blood pressure in pregnant rats, since pregnant normotensive SD rats did not show any decrease of control blood pressure and their response to each dose of both agents was also reduced. Furthermore, the sensitivity to both vasoconstrictors was decreased in pregnant rats of each strain by comparison to non-pregnant rats. In conclusion, vascular reactivity to both All and AVP decreases during gestation.

Influence of hot environment on body temperature, heart rate and blood pressure of pregnant rats

Twenty-six out of fifty pregnant rats died on days 18-20 of gestation at 33 degrees C environment. The death generally occurred in the dark period around 1-5 a.m. Shortly prior to the death, very high body temperature of 42.0-43.7 degrees C were recorded and the blood pressure was undetectably low. In autopsy, the finding in the main was the congestion in lungs and liver. In temporal changes of body temperature and heart rate, influences of hot environment were observed, but there was no significant difference between dead pregnant group and delivered pregnant group at 33 degrees C environment. At 23 degrees C, the blood pressure of pregnant rats starting at about 140 mmHg level, reached 160-168 mmHg on day 12 of gestation and maintained the level to day 16. On day 18, the pressure returned to 140-145 mmHg and unchanged to term. At 33 degrees C, significant differences were obviously observed between dead group and delivered group in temporal changes of blood pressure. The blood pressure of rats delivered sharply increased to 170 mmHg or more in the middle stage of pregnancy and decreased to about 140 mmHg in the final stage. However, these of dead group increased to 160 mmHg or less in the middle stage of pregnancy, and maintained the level until the final stage.

Influence of blood pressure control on delivery in pregnant rats in a warm environment

The relation between blood pressure and delivery in pregnant rats was investigated when the blood pressure of pregnant rats was controlled by a pressor or antihypertensive drug in the middle or final stage of pregnancy. All of the pregnant rats studied delivered in a 23 degrees C environment in spite of blood pressure control by a pressor or antihypertensive drug. At 33 degrees C, the pregnant rats were divided into two groups whose blood pressure was increased severely (160-175 mm Hg) or moderately (145-155 mm Hg) at 10 days of pregnancy. Those in the former group delivered, but those in the latter died in the final stage of pregnancy. When the pregnant rats in the group with high blood pressure on day 10 were treated with a antihypertensive drug in the middle stage of pregnancy or with a pressor drug in the final stage, the mortality rate was 100 per cent in both cases. The delivery rate was 57 per cent when the pregnant rats were treated with a antihypertensive drug from the middle to the final stage of pregnancy. In the group with low blood pressure on day 10, all of the pregnant rats delivered when they were treated with a pressor drug in the middle stage of pregnancy. However, the delivery rate was 89 per cent when the pregnant rats were treated with antihypertensive drug in the final stage of pregnancy.