Hypertensive Dams Research Articles

Maternal EGCG intervention mitigates chronic hypertension during pregnancy in spontaneously hypertensive rats without adverse effects on pregnancy outcomes

Background: Chronic hypertension during pregnancy is a significant concern, associated with increased risks of maternal-fetal morbidity and mortality. Epigallocatechin gallate (EGCG), a compound known for its cardioprotective properties, has gained attention as a potential health supplement due to its favorable safety profile. Objective: This study aims to investigate the effects of maternal EGCG supplementation on elevated blood pressure and pregnancy outcomes in a rodent model of chronic hypertension, specifically using spontaneously hypertensive rats (SHR). Furthermore, the study explores the influence of maternal EGCG supplementation on the blood pressure of SHR offspring during early postnatal development. Methods: SHR dams received oral EGCG at 30 mg/kg body weight. Systolic blood pressure (SBP) monitored weekly throughout gestation period and until postpartum day 21. Pregnancy outcomes - litter size, pup viability, and birth weights - were recorded. SBP in weaned SHR offspring was monitored from 5 to 13 weeks of age to assess long-term effects of maternal EGCG treatment. Daily cage-side observations evaluated general health, behavior, and signs of toxicity. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine were analyzed to evaluate liver and kidney function. Results: EGCG treatment in SHR dams progressively reduced maternal SBP throughout gestation and the postpartum period. However, EGCG administration did not affect pregnancy outcomes (gestation duration, litter size, and birth weights). Markers of liver and kidney function (ALT, AST, urea, and creatinine) showed no signs of organ injury in EGCG-treated groups. Contrary to expectations, SBP in SHR offspring exposed to perinatal EGCG did not decrease compared to control groups, indicating maternal EGCG did not alter the offspring's hypertension predisposition. Conclusion: Maternal EGCG supplementation effectively lowered blood pressure in hypertensive dams without compromising pregnancy outcomes or causing liver and kidney damage. These findings suggest that EGCG may be a safe cardioprotective supplement during pregnancy. However, perinatal EGCG exposure did not alter the inherent genetic predisposition to hypertension in SHR offspring. Keywords: Theaceae; Camellia sinensis; green tea; catechins, EGCG; hypertension, pregnancy outcomes, perinatal, spontaneously hypertensive rats, chronic hypertension during pregnancy

Maternal immune suppression during pregnancy does not prevent abnormal behavior in offspring

BackgroundOffspring of hypertensive disorders of pregnancy are at an increased risk of developing neurodevelopmental and neurobehavioral disorders compared to offspring from non-affected pregnancies. Using rodent models of Preeclampsia (PreE; new onset of hypertension after 20 weeks gestation) and HELLP (hemolysis, elevated liver enzymes, and low platelets), we studied the behavioral outcome of their offspring in adolescence.MethodsA subset of dams received Orencia, a T-cell activation inhibitor, as T cells have been associated with the induction of hypertension and inflammation during pregnancy. We hypothesized that offspring from hypertensive dams would experience adverse behavioral outcomes in social, cognitive, locomotor, and anxiety tests, and offspring from dams treated with Orencia would demonstrate less adverse behaviors.ResultsMale offspring of PreE + Orencia dams (p < 0.05) and female offspring from HELLP + Orencia dams (p < 0.05) spent more time playing compared to normal pregnant offspring. All offspring from hypertensive and Orencia-treated dams performed worse on the Barnes Maze test compared to normal pregnant. We also measured adult (postnatal day > 60) myelin basic protein (MBP) and NeuN expression in both the prefrontal cortex and hippocampus. In the hippocampus and prefrontal cortex, there was no difference in expression of either MBP or NeuN in all groups regardless of sex.ConclusionThe results from this study suggest that offspring of hypertensive disorders of pregnancy have behavioral changes, specifically cognitive differences. This study has shown that there is a sex dependent difference in offspring neurobehavioral development, influenced in part by the type of hypertensive disorder of pregnancy, and alterations in the maternal immune system.

Voluntary Exercise Eliminates Maternal Gestational Hypertension-Induced Hypertensive Response Sensitization to Postweaning High-Fat Diet in Male Adult Offspring.

Exercise has profound effects on cardiovascular function and metabolism in both physiological and pathophysiological states. The present study tested whether voluntary exercise would protect male offspring against maternal gestational hypertension-induced hypertensive response sensitization elicited by post-weaning high-fat diet (HFD). On low-lard-fat diet, offspring of both normotensive and hypertensive dams had comparable resting blood pressure, but HFD feeding elicited an enhanced increase in blood pressure (ie, hypertensive response sensitization) in sedentary offspring of hypertensive dams when compared with sedentary offspring of normotensive dams. The HFD fed sedentary offspring of hypertensive dams displayed greater sympathetic activity, enhanced pressor responses to centrally administered ANG II (angiotensin II) or leptin, and greater mRNA expression of proinflammatory cytokines, leptin, and a marker of blood-brain barrier leakage in the hypothalamic paraventricular nucleus. The enhanced blood pressure and central sympathetic activity in HFD-fed sedentary offspring of hypertensive dams were significantly reduced by exercise but fell only to levels comparable to HFD-fed exercising offspring of normotensive dams. HFD-induced increases in plasma IL-6 (interleukin-6) and sympathetic activity and greater pressor responses to central TNF (tumor necrosis factor)-α in offspring from both normotensive and hypertensive dams were also maintained after exercise. Nevertheless, exercise had remarkably beneficial effects on metabolic and autonomic function, brain reactivity to ANG II and leptin and gene expression of brain prohypertensive factors in all offspring. Voluntary exercise plays a beneficial role in preventing maternal hypertension-induced hypertensive response sensitization, and that this is associated with attenuation of enhanced brain reactivity and centrally driven sympathetic activity.

Evidence of Anxiety, Depression and Learning Impairments following Prenatal Hypertension.

Background: Hypertensive disorders of pregnancy, such as Preeclampsia (PreE) and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome, affects approximately 5–10% of pregnancies and increases the risk of women developing disorders, such as anxiety or depression, in the postpartum period. Using preclinical rodent models, we set out to determine whether rats with a history of PreE or HELLP had evidence of anxiety, depression or cognitive impairment and whether immune suppression during pregnancy prevented these changes in mood and/or cognition. Methods: Timed-pregnant rats were infused with sFlt-1 and/or sEng to induce PreE or HELLP beginning on gestational day 12. After delivery, a battery of validated behavioral assays was used to assess post-partum depression, anxiety and learning. Results: There was no negative effect on maternal pup interaction due to PreE or HELLP; however, hypertensive dams spent more time immobile in the forced swim test (p < 0.0001). Hypertensive dams also spent less time in the open area of the open field (p = 0.001). There were no significant changes in recognition memory (p = 0.08); however, spatial learning was impaired in hypertensive dams (p = 0.003). Immobility time in the forced swim test was positively correlated with increased circulating S100B (p = 0.04), while increased time spent in the outer zones of the open field was negatively correlated with BDNF levels (p < 0.0001). Conclusion: The results from this study suggest that hypertensive pregnancy disorders are associated with depression, anxiety and learning impairments in the post-partum period.

Maternal Angiotensin II-Induced Hypertension Sensitizes Postweaning High-Fat Diet-Elicited Hypertensive Response Through Increased Brain Reactivity in Rat Offspring.

BackgroundPrenatal and postnatal insults can induce a physiological state that leaves offspring later in life vulnerable to subsequent challenges (stressors) eliciting cardiometabolic diseases including hypertension. In this study, we investigated whether maternal angiotensin II–induced hypertension in rats sensitizes postweaning high‐fat diet (HFD)‐elicited hypertensive response and whether this is associated with autonomic dysfunction and altered central mechanisms controlling sympathetic tone in offspring.Methods and ResultsWhen eating a low‐lard‐fat diet, basal mean arterial pressure of male offspring of normotensive or hypertensive dams were comparable. However, HFD feeding significantly increased mean arterial pressure in offspring of normotensive and hypertensive dams, but the elevated mean arterial pressure induced by HFD was greater in offspring of hypertensive dams, which was accompanied by greater sympathetic tone and enhanced pressor responses to centrally administrated angiotensin II or leptin. HFD feeding also produced comparable elevations in cardiac sympathetic activity and plasma levels of angiotensin II, interleukin‐6, and leptin in offspring of normotensive and hypertensive dams. Reverse transcriptase polymerase chain reaction analyses in key forebrain regions implicated in the control of sympathetic tone and blood pressure indicated that HFD feeding led to greater increases in mRNA expression of leptin, several components of the renin‐angiotensin system and proinflammatory cytokines in offspring of hypertensive dams when compared with offspring of normotensive dams.ConclusionsThe results indicate that maternal hypertension sensitized male adult offspring to HFD‐induced hypertension. Increased expression of renin‐angiotensin system components and proinflammatory cytokines, elevated brain reactivity to pressor stimuli, and augmented sympathetic drive to the cardiovascular system likely contributed.

Maternal Supplementation of Inositols, Fucoxanthin, and Hydroxytyrosol in Pregnant Murine Models of Hypertension.

Myoinositol (M) and D-chiro-inositol (D) are insulin sensitizer compounds, while fucoxanthin (F) and hydroxytyrosol (H) are antioxidant substances. We aim to investigate if the combination of these compounds, will improve the vascular responses in pregnant mouse models of hypertension: a genetic model, transgenic heterozygous mice lacking endothelial nitric oxide synthase gene (eNOS-/+); and environmental, wild-type (WT) mice. Those mouse models will allow a better understanding of the genetic/environmental contribution to hypertension in pregnancy. eNOS-/+ and WT female were fed high fat diet for 4 weeks, then at 7-8 weeks of age were mated with WT male. On gestational day (GD) 1, they were randomly allocated to receive MDFH treatment or water as control: eNOS-/+ MDFH (n = 13), eNOS-/+ (n = 13), WT-MDFH (n = 14), and WT (n = 20). Systolic blood pressure (SBP) was obtained at GD 18, then dams were sacrificed; fetuses and placentas collected, and 2 mm segments of carotid arteries isolated for vascular responses using the wire-myograph system. Responses to phenylephrine (PE), with/without the NOS inhibitor (N-nitro-l-arginine methyl ester (l-NAME)), and to acetylcholine (Ach) and sodium nitroprussiate (SNP) were performed. SBP decreased in eNOS-/+ and WT dams after MDFH supplementation. In eNOS-/+, MDFH lower the contractile response to PE and l-NAME and improved Ach vasorelaxation. In WT dams, MDFH treatment did not affect PE response; MDFH treatment lowered the vascular PE response after incubation with l-NAME. No differences were seen in SNP relaxation in both models. MDFH decreased SBP in both genetically and environmentally hypertensive dams and improved vascular responses mostly in the eNOS-/+ dams.

Parental Renovascular Hypertension-Induced Autonomic Dysfunction in Male Offspring Is Improved by Prenatal or Postnatal Treatment With Hydrogen Sulfide.

Increasing evidence indicates there is a strong association between parental health during pregnancy and incidence of cardiovascular disease in adult offspring. Recently, hydrogen sulfide (H2S) has been demonstrated to be a powerful vasodilator of the placental vasculature, improving intrauterine growth restriction. In this study, we investigated whether parental hypertension induces autonomic dysfunction in male adult offspring, and the H2S mechanism underlying this autonomic dysfunction. 2-kidney-1-clip method was employed to induce parental hypertension during pregnancy and lactation in rats. Basal blood pressure (BP) and autonomic function of male offspring in adulthood was evaluated. Additionally, either maternal hypertensive dams or their male offspring after weaning were treated with H2S to determine improving effects of H2S on autonomic dysfunction. The BP was significantly increased in male offspring of renovascular hypertensive dams when compared to that in offspring of normotensive dams. The offspring of renovascular hypertensive dams also exhibited blunted baroreflex sensitivity, increased sympathetic effect and sympathetic tonus. Western blotting analysis revealed downregulation of endogenous H2S catalyzed enzyme and upregulation of angiotensin Ang II type 1 receptor (AT1R) pathway in the nucleus tractus solitarius and rostral ventrolateral medulla, two hindbrain nuclei involved in BP and autonomic regulation, in these offspring. Either prenatal or postnatal treatment with H2S improved the adverse effects. The results suggest that parental hypertension results in elevated BP and autonomic dysfunction in adult male offspring through activation of AT1R pathway and inhibition of endogenous H2S production in the brain.

Social stress-induced blood pressure increase in borderline hypertensive rats is associated with endothelial dysfunction in the resistant arteries

ObjectivesSeveral studies have observed that altered endothelial function is involved in the development of stress-induced hypertension. The aim of this study was to investigate the effects of chronic social stress (crowding) on endothelium-dependent relaxation (EDR) of the superior mesenteric artery (SMA) and of small resistant mesenteric arteries (MA) as well as on neurogenic contractions of SMA in adult borderline hypertensive rats (BHR).MethodsTwelve-week-old BHR (offspring of spontaneously hypertensive dams and Wistar-Kyoto sires) males were exposed to crowding (living space: 200 cm2/rat) for eight weeks. Control BHR were kept in the groups of four rats per cage (living space: 480 cm2/rat). Systolic blood pressure (sBP) was determined by the tail-cuff method.Vascular function was investigated in the isolated arteries at isometric conditions.EDR was assessed using acetylcholine test.ResultsCrowding significantly increased sBP of BHR to the hypertensive values. Results showed that stress did not affect total acetylcholine-induced relaxation and its nitric oxide (NO)-dependent and NO-independent components in the SMA. In the resistant MA, stress reduced total acetylcholine-induced relaxation by reducing NO-independent component, without the alterations of its NO-dependent component.However, stress failed to affect significantly neurogenic contractions of SMA elicited by electrical stimulation of perivascular sympathetic nerves and vasoconstriction induced by exogenous noradrenaline in SMA.ConclusionIn conclusion, chronic social stress can accelerate the development of hypertension in BHR, which seems to be associated with NO-independent endothelial dysfunction in small resistant arteries.Supported by the grants VEGA No. 2/0190/17 and APVV-16-0263.

High-fat diet reduces weight gain but increases other cardio-metabolic indices in offspring of normotensive and hypertensive rats

This study investigated the effect of post-natal consumption of high-fat diet (HFD) on cardio-metabolic indices in male offspring of hypertensive female rats. There were neither significant differences in body weight gain either in pups from normotensive or hypertensive dams that received normal diet during the post-weaning periods (except at 7th and 9th weeks), nor in both pup groups that received HFD. However, both pup groups that received HFD had reduced body weight gain when compared to their counterparts that received normal diet. Post-weaning administration of HFD to pups of hypertensive and normotensive dams significantly increased their blood glucose, pressure and lipid profiles when compared to those weaned to normal diet. It was concluded that male offspring consumption of HFD diet elicits cardio-metabolic disturbance that slightly depended of maternal cardiovascular status but majorly depended on post-weaning weight gain, while that elicited by maternal hypertension is not related to post-weaning weight gain.

Maternal Renovascular Hypertensive Rats Treatment With Hydrogen Sulfide Increased the Methylation of AT1b Gene in Offspring.

A large number of studies have shown hypertension of offspring in adulthood is related to parental health during pregnancy. Hydrogen sulfide (H2S) could relax placental vasculature and improve intrauterine growth restriction. In the present study, we want to observe the effect of H2S on the fetal programming of renovascular hypertension, a rat model of secondary hypertension. Renovascular hypertension was induced by 2-kidney-1-clip, their adult pups were used to evaluate basal blood pressure. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured noninvasively by tail-cuff plethysmography in conscious offspring; HE staining was used to observe morphology of kidney; the protein expression of angiotensin II receptor 1 (AT1R) tested by western blot; methylation of angiotensin II receptor 1b (AT1b) gene used pBLUE-T-cloning to check. The SBP and DBP in the offspring of renovascular hypertensive dams were higher than those in control group. Moreover, interstitial inflammatory infiltration was significant in the kidney and the protein expression of AT1R was also increased in the offspring of renovascular hypertensive dams. Conversely, methylation of AT1b promoter (U01033 277-1611) decreased in the first 3 CG sites. Either prenatal or postnatal treatment with H2S could increase the methylation of AT1b and downregulate AT1R expression then improve the blood pressure. These results suggested that parental secondary hypertension-induced kidney damage that elevated basal blood pressure in adult offspring. Prenatal or postnatal administration with H2S induced improved effect accompanied by an increased methylation of AT1b gene then downregulated protein of AT1R in offspring.

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring.

Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams. Most of these increases were significantly inhibited by either renal denervation performed at 8 weeks of age or treatment with an angiotensin-converting enzyme inhibitor, captopril, in drinking water starting at weaning. When tested beginning at 10 weeks of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA expression of RAAS components and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented pressor response in male offspring of hypertensive dams. The augmented blood pressure change and most of the increases in gene expression in the offspring were abolished by either renal denervation or captopril. The results suggest that maternal hypertension during pregnancy enhances pressor responses to angiotensin II through overactivity of renal nerves and the RAAS in male offspring and that upregulation of the brain RAAS and proinflammatory cytokines in these offspring may contribute to maternal gestational hypertension-induced sensitization of the hypertensive response to angiotensin II.

The effect of combined inositol supplementation on maternal metabolic profile in pregnancies complicated by metabolic syndrome and obesity

Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype. The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model. Female heterozygous endothelial nitric oxide synthase(-/+) mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol-treated vs metabolic-like syndrome-nontreated mice and obese-myoinositol/D-chiroinositol-treated vs obese nontreated mice. Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo (P= .04), whereas there was no difference in systolic blood pressure between treated and placebo-treated obese pregnant mice. Pregnant metabolic-like syndrome mice treated with myoinositol/D-chiroinositol showed lower glucose values during the glucose tolerance test and in the area under the curve (myoinositol/D-chiroinositol: 17512.5 ± 3984.4 vs placebo: 29687.14 ± 8258.7; P=.003), but no differences were seen in the obese pregnant mice. Leptin serum levels were lower in the metabolic-like syndrome-myoinositol/D-chiroinositol-treated mice compared with the placebo group (myoinositol/D-chiroinositol: 16985 ± 976.4 pg/dL vs placebo: 24181.9 ± 3128.2 pg/dL, P= .045). No other differences were seen in any of the remaining serum metabolic biomarkers studied in metabolic-like syndrome and in obese pregnant mice. Maternal weight gain was not different in the pregnant metabolic-like syndrome dams, whereas it was lower in the obese myoinositol/D-chiroinositol-treated dams compared with the placebo group (myoinositol/D-chiroinositol: 10.9 ± 0.5 g vs 12.6 ± 0.6 g, P= .04). Fetal and placental weights did not differ between myoinositol/D-chiroinositol-treated and nontreated pregnant dams with metabolic-like syndrome and obesity. Combined inositol treatment during pregnancy improves blood pressure, glucose levels at the glucose tolerance test, and leptin levels in pregnant dams with metabolic-like syndrome phenotype but not in obese pregnant dams. In addition, inositol treatment was associated with lower gestational weight gain in the obese but not in the metabolic-like syndrome pregnant dams.

Sensitization of angiotensin (ANG) II‐elicited hypertension in offspring of hypertensive pregnant rats: evidence of sex differences

Recent findings demonstrate that there is association between maternal health status during pregnancy and cardiovascular disease of adult offspring. The purpose of the present study was to test whether maternal hypertension produced by ANG II infusion (200 ng/kg/min, sc) during pregnancy sensitizes ANG II-induced increase in blood pressure (BP) in adult offspring, and whether there are male or female differences. Aortic BP and heart rate (HR) were measured in dams and their offspring by telemetry. When tested beginning at 10 weeks of age, male offspring of hypertensive dams showed an enhanced hypertensive response to sc ANG II (120 ng/kg/min, Δ41.6±2.6 mmHg) compared to male offspring of normotensive dams (Δ17.1±1.3 mmHg). In females, ANG II treatment produced only a slight, but significant increase in BP in offspring of either hypertensive (Δ7.5±2.5 mmHg) or normotensive dams (Δ11.6±2.5 mmHg). The enhanced increase in BP in male offspring from hypertensive dams was attenuated by renal denervation performed at 8 weeks of age (Δ29.3 ±2.6 mmHg). RT-PCR analysis of the lamina terminalis and the paraventricular nucleus tissues indicated upregulation of mRNA expression of RAS components and proinflammatory cytokines, including renin, angiotensinogen, mineralocorticoid receptor, interleukin (IL)-6 and IL-1β in male, but not female, offspring from hypertensive dams. The results suggest that maternal hypertension during pregnancy enhances pressor responses to ANG II through upregulation of the brain RAS and inflammatory cytokines in male offspring, and that female offspring are protected from these effects.

Maternal hypertension during pregnancy modifies the response of the immature brain to hypoxia–ischemia: Sequential MRI and behavioral investigations

Hypoxic–ischemic (HI) brain injury occurring during the perinatal period is still a major cause of mortality and morbidity. We assessed the impact of maternal hypertension, the most common medical disorder of pregnancy, on the anatomical and functional consequences of HI insult in the immature brain. Rat pups from spontaneously hypertensive (SHR) and normotensive (Wistar Kyoto — WKY) dams were subjected to HI brain damage at post-natal day 7 (P7). Brain lesion and functional deficits were analyzed from 10min to 35days after HI, using magnetic resonance imaging (MRI), sensorimotor and cognitive tests. MRI data revealed that SHR pups displayed less brain damage than WKY, attested by an initial smaller lesion followed by a reduced tissue loss at chronic stage (57.1±21.6 and 31.1±27% ipsilateral hemisphere atrophy in WKY and SHR, respectively). Behavioral analyses showed less HI-induced behavioral deficits in motor coordination (rotarod test) and spatial learning (Morris water maze test) in pups from hypertensive dams compared to those from normotensive ones. The data suggest that maternal hypertension causes prenatal stress that may render the immature brain more resistant to subsequent hypoxia–ischemia, related to a preconditioning phenomenon.

Inflammatory cytokines are elevated in intrauterine growth restricted offspring in response to placental insufficiency.

Numerous epidemiological studies report a link between intrauterine growth restriction (IUGR) and hypertension. Our laboratory utilizes a unique model of IUGR by inducing placental insufficiency in the rat during late gestation. The response to placental ischemia in the pregnant rat is characterized by hypertension associated with endothelial dysfunction accompanied by increased inflammatory cytokines, mimicking the maternal syndrome of preeclampsia. Offspring born of the hypertensive dams exhibit IUGR and develop an increase in blood pressure (BP) by 4 weeks of age. We hypothesized that elevated inflammatory cytokines may be a contributing factor to the increased BP in IUGR offspring. We examined the circulating cytokine profile, via cytokine protein array analysis, in plasma of IUGR and control offspring at 4 weeks of age. Approximately 60% of all cytokines examined were significantly up‐regulated in IUGR offspring compared to control offspring. The increase in Interferon gamma, Interleukin‐1, and macrophage inflammatory protein are characteristic of endothelial dysfunction which could contribute to the development of the hypertension in the IUGR offspring. In conclusion, the circulating cytokine profile which is significantly altered in IUGR offspring compared to control offspring may be indicative of chronic inflammation associated with IUGR in response to placental insufficiency.

Cardiovascular Correlates of Predisposition to Hypertension in Pups of one Kidney: One Clip Renal Hypertensive Dams

We reported that the pups of one kidney:one-clip Goldblatt hypertensive (HT) rats have a predisposition to the induction of experimental hypertension. To investigate the nature of the predisposition, pups of HT dams were challenged with vasopressor agents at 28-days-of-age or treated with DOCA and 6.5% salt diet between 35 and 81 days-of-age. Pups of HT dams had a significantly greater blood pressure between 28 and 81 days-of-age and also showed a greater change in blood pressure when provided a 6.5% salt diet than did pups of normotensive dams. Pups of HT dams demonstrated a decreased bradycardic response after injection of angiotensin II (p less than .05) and a lesser change in mean arterial blood pressure after injection of angiotensin II or norepinephrine than did the pups from normotensive dams. These results suggest an effect of maternal hypertension on the development of cardiovascular control mechanisms in her offspring. The decreased pressor response suggests the predisposition is not due to an increased vascular sensitivity to vasopressors.

Predisposition to hypertension in rat pups from renal hypertensive dams.

We determined that a predisposition to hypertension could be transmitted by a nongenetic, renal hypertensive (HT) mother to her pups. The pups of one-kidney: one clip Goldblatt (1K:1C) hypertensive female rats and of sham operated normotensive female rats were subjected to the 1K:1C procedure at 28 days of age and tail cuff blood pressures (BP) were determined. After surgical induction of hypertension, HT male pups of HT dams had a significantly greater (p less than .05) BP by 14 days after surgery (194 +/- 8 mm Hg) than did HT male pups of normotensive (NT) dams (169 +/- 6 mm Hg). A similar trend (p less than .08) was observed for the HT female pups of HT dams (185 +/- 7 mm Hg) compared to HT females from NT dams (163 +/- 4 mm Hg). Thus, in utero exposure of pups to a chronic HT state alters the response of the pups to the surgical induction of hypertension. Furthermore, the results suggest that transfer of a predisposition to hypertension from mother to offspring occurred during the pregnancy/lactation period.