Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction

In low sodium-induced intrauterine growth restricted (IUGR) rat, foetal adrenal steroidogenesis as well as the adult renin– angiotensin–aldosterone system (RAAS) is altered. The aim of the present study was to determine the expression of cytochrome P450 aldosterone synthase (P450aldo) and of angiotensin II receptor subtypes 1 (AT1R) and 2 (AT2R) in adult adrenal glands and whether this expression could be influenced by IUGR and by high-salt intake in a sex-specific manner. After 6 weeks of 0.9% NaCl supplementation, plasma renin activity, P450aldo expression and serum aldosterone levels were decreased in all groups. In males, IUGR induced an increase in AT1R, AT2R, and P450aldo levels, without changes in morphological appearance of the zona glomerulosa (ZG). By contrast, in females, IUGR had no effect on the expression of AT1R, but increased AT2R mRNA while decreasing protein expression of AT2R and P450aldo. In males, salt intake in IUGR rats reduced both AT1R mRNA and protein, while for AT2R, mRNA levels decreased whereas protein expression increased. In females, salt intake reduced ZG size in IUGR but had no affect on AT1 Ro r AT 2R expression in either group. These results indicate that, in response to IUGR and subsequently to salt intake, P450aldo, AT1R, and AT2R levels are differentially expressed in males and females. However, despite these adrenal changes, adult IUGR rats display adequate physiological and adrenal responses to high-salt intake, via RAAS inhibition, thus suggesting that extra-adrenal factors likely compensate for ZG alterations induced by IUGR.