Maternal angiotensin II‐induced hypertension impairs salt sensitivity and estrogen regulation of salt/water intakes in female adult offspring

Abstract

Blood pressure (BP) is associated with body fluid homeostasis and the intake and excretion of water and salt. Female sex hormones play an important role in regulating salt and water intake. Recent evidence indicates that prenatal insults can have a strong influence on BP salt sensitivity in offspring. In this study, we investigated if maternal angiotensin II‐induced hypertension (MHT) alters BP salt sensitivity in female offspring exposed post‐weaning to a high salt diet (HSD, 4% salt, 12 weeks), and if estrogen modulates the HSD‐induced changes in BP and salt/water intake. Post‐weaning HSD feeding elicited a significant increase in BP in intact female offspring of normotensive (NT) dams when compared with normal salt diet (NSD) fed female offspring (MAP, 114.5±0.7 to 124.1±1.6 mmHg). However, HSD feeding did not alter BP in intact female offspring of MHT dams (MAP, 114.7±1.7 to 110.6±1.2 mmHg), indicating that MHT blunted salt sensitivity in the offspring. Ovariectomy (OVX) diminished the HSD‐induced BP increase in offspring of NT dams (111.2±1.6 mmHg) but surprisingly significantly increased BP in HSD fed offspring of MHT dams (118.5±1.2 mmHg). There were no differences in HSD and water intakes and body fluid composition (measured by nuclear magnetic resonance spectroscopy) between intact offspring of NT and MHT dams. OVX in offspring of NT dams resulted in significant increases in the intake of HSD and water, and in body fluid composition. The offspring of MHT dams had only a slight increase in HSD intake (i.e., less than that of offspring of NT dams), and they had no changes in water intake or body fluid composition. This suggests that estrogen effects on salt and water intakes were compromised by MHT. The results indicate that MHT induced by angiotensin II during pregnancy may downregulate salt sensitivity and compromise the regulatory action of estrogen to salt and water intakes, thereby altering the BP response to HSD. It is notable that these results seem to be contrary to current dogma that prenatal insults sensitize the development of hypertension and that estrogen plays protective role. These observations need further investigation.