Prenatal dehydration alters renin–angiotensin system associated with angiotensin-increased blood pressure in young offspring

Abstract

The renin–angiotensin system (RAS) has an important role in cardiovascular homeostasis. This study determined the influence of water deprivation during pregnancy on the development of the RAS in rats, and examined blood pressure (BP) in the adolescent offspring. Pregnant rats were water deprived for 3 days at late gestation, and we examined fetal cardiac ultrastructure, as well as heart angiotensin (Ang) II receptor protein and mRNA, liver angiotensinogen and plasma Ang II concentrations. We also tested cardiovascular responses to i.v. Ang II in the young offspring. In utero exposure to maternal water deprivation significantly decreased fetal body and heart weight, and increased fetal plasma sodium and osmolality. Fetal liver angiotensinogen mRNA, plasma Ang I and Ang II concentrations were also increased. Although fetal AT1a and AT1b receptor mRNA and AT1 protein were not changed, AT2 receptor mRNA and protein levels in the heart were significantly increased following maternal dehydration. Prenatal exposure to maternal water deprivation had no effect on baseline BP; however, it significantly increased BP in response to i.v. Ang II infusion, and decreased baroreflex sensitivity in the offspring. In addition, the heart AT2 receptor mRNA and protein were higher in the offspring exposed to prenatal dehydration. The results of this study demonstrate that prenatal dehydration affected the RAS development associated with an Ang II-increased BP in fetal origin.

Epigenetics, essential hypertension and renin–angiotensin system upregulation in the offspring of water-deprived pregnant rats

“…The study by Guan et al 6 seems to provide a plausible mechanism for the higher fetal angiotensin levels by suggesting that maternal water deprivation, with plasma hypertonicity, increased placental osmotic gradient and fetal plasma osmolality, may be a stimulus for the upregulation of the fetal renin-angiotensin system. The effects of administering hypertonic solutions and ethanol, to mothers during pregnancy, on the fetal renin-angiotensin system have not been systematically studied.…”

“…The article by Guan et al 6 makes an important contribution to this effort. Water deprivation is a stimulus to the renin-angiotensin system, and renin-angiotensin system activators administered to rodent mothers during pregnancy have been shown to affect the development of thirst threshold in their offspring.…”

“…The study by Guan et al 6 has demonstrated the potential for such a persistent defect in renin-angiotensin regulation of blood pressure resulting from prenatal exposure to maternal water deprivation for 3 days during late gestation. Guan et al 6 have documented increased hepatic angiotensinogen mRNA, plasma angiotensin I and II levels; expression of angiotenisn-2 receptors and exaggerated responsiveness to administration of angiotensin with decreased baroreceptor reflex sensitivity in the offspring.…”

“…Guan et al 6 have documented increased hepatic angiotensinogen mRNA, plasma angiotensin I and II levels; expression of angiotenisn-2 receptors and exaggerated responsiveness to administration of angiotensin with decreased baroreceptor reflex sensitivity in the offspring. High plasma renin activity has been reported in 10-20% of individuals diagnosed with essential hypertension in the absence of water deprivation.…”

“…Moreover, the greater genetic diversity observed in African Americans than in Caucasians and other US sub-populations seems to argue against a purely genetic basis for an African-American predilection for hypertension. 13 The study by Guan et al 6 suggests an epigenetic mechanism. Certain resurrection plants are known to possess gene products that impart an exquisite resistance to desiccation, exhibited by survival after a 96% water loss.…”