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

Abstract

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.