Prenatal exposure to angiotensin II increases blood pressure and decreases salt sensitivity in rats

Abstract

Renin angiotensin aldosterone system (RAAS) plays an essential role in the homeostatic control of arterial blood pressure, perfusion of tissues, and control of extracellular fluid. Its components are highly expressed in the developing kidney, general vasculature, brain, and heart. A modified intrauterine environment alters mechanisms controlling blood pressure (BP) and can lead to hypertension in the adult offspring and developmentally programmed RAAS can be involved in this process. There are very little data about the effects of increased angiotensin II (Ang II) concentrations during pregnancy on in utero development of the fetus. In our study, we administered Ang II to pregnant female rats via osmotic mini-pumps and evaluated the postnatal development and BP control in the offspring. To estimate possible developmental changes in sensitivity to salt, we exposed the offspring to a diet with increased salt content and measured plasma aldosterone levels and plasma renin activity. Increased Ang II during pregnancy raised BP in the offspring; however, salt sensitivity was decreased in comparison to controls. Relative weight of the left ventricle was decreased in the offspring prenatally exposed to Ang II, while relative kidney weight was reduced only in female offspring. Prenatal treatment led to increased aldosterone levels and decreased plasma renin activity, suggesting a complex physiological response. Our results suggest that conditions leading to upregulation of RAAS during pregnancy can influence the cardiovascular system of the fetus and have a long-term impact on the offspring's health.

Effect of maternal renin-angiotensin-aldosterone system activation on social coping strategies and gene expression of oxytocin and vasopressin in the brain of rat offspring in adulthood

“…In our study, AngII animals have been reported to have increased plasma aldosterone levels compared to controls (Svitok et al 2017), also observed in transgenic rats (TGR(mRen2)27) with upregulated RAAS. Aldosterone levels were found to be 10-times higher in rats with upregulated RAAS than in control rats, which supports upregulation of the renin-angiotensin system, as it is well known that angiotensin II stimulates aldosterone synthesis (Ferrario 1983;Zeman et al 2007).…”

“…research presented here is part of a larger project focused on the effects of prenatal activation of regulatory mechanisms of blood pressure, part of which has already been published (Svitok et al 2017). We hypothesised that the activation of maternal RAAS (via higher levels of angiotensin II) would be associated with changes in the social coping behaviour of the offspring.…”

“…However, foetal exposure to ACE inhibitors and/or AT1 receptor antagonist has been associated with multiple developmental defects or even intrauterine foetal death (Quan 2006;Bullo et al 2012). On the other hand, very little data has been provided about the effects of increased angiotensin II concentrations during pregnancy on in utero development of the foetus (Svitok et al 2017).…”

Renal impairment induced by prenatal exposure to angiotensin II in male rat offspring

“…However, we did not find significant changes in the kidney after increased salt intake and this finding is in agreement with data on BP in our previous study. 18 Surprisingly, the progeny of Ang II treated mothers displayed a decreased sensitivity of BP to salt. The absence of negative effects of higher salt diet was not expected but can be explained by a moderately increased (2%) salt content, which is still in a physiological range.…”

“…17 Moreover, in our previous study we demonstrated that exposure of pregnant rats to increased Ang II altered postnatal development and increased BP in offspring. 18 These changes were associated with increased aldosterone levels and decreased renin activity in the circulation, 18 but physiological mechanisms behind this phenomenon are not fully explained. Angiotensin II increases expression of cytokines, inflammatory and fibrotic factors that affect renal hemodynamics, and leads to the development of glomerular damage.…”