OPPOSITE FEEDBACK-CONTROL OF RENIN AND ALDOSTERONE BIOSYNTHESIS IN THE ADRENAL-CORTEX BY ANGIOTENSIN-II AT(1)-SUBTYPE RECEPTORS

The aims of this study were to identify whether tissue renin is regula ted by a negative-feedback mechanism produced by locally generated ang iotensin (Ang II) in the adrenal cortex and to detect the pathway of A ng II modulation. For this purpose, in 36 12-week old, salt-restricted , nephrectomized Sprague-Dawley rats, we studied the effects of the An g II AT(1)-subtype receptor antagonist losartan and of the Ang II AT(2 )-subtype receptor antagonist PD123319 on renin mRNA and activity, ald osterone synthase mRNA, and AT(1a)-, AT(1b)-, and AT(2)-subtype recept or expression in the adrenal cortex. Ten additional rats, kept on a re gular diet and then nephrectomized, were also studied. In salt-restric ted, nephrectomized rats, losartan administration caused increases of adrenal renin mRNA (P < .05) and activity (P < .05) and a concomitant reduction of aldosterone synthase mRNA (P < .05). In addition, after l osartan AT(1b), receptor mRNA was reduced (P < .05), AT(1a) receptor m RNA was unchanged, and AT(2) mRNA was increased (P < .05). PD123319 di d not significantly modify any of these parameters. In conclusion, in salt-restricted, nephrectomized rats, selective antagonism of AT(1)-su btype receptors stimulates the expression and the activity of renin in the adrenal cortex. This observation demonstrates that Ang II locally formed in the adrenal cortex exerts a modulatory negative-feedback ac tion on adrenal renin biosynthesis independent of the influence of the circulating renin-Ang system; this action is largely mediated through the AT(1b)-subtype receptors.