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(Hypertension. 1997;30:563.)
© 1997 American Heart Association, Inc.

Articles

Opposite Feedback Control of Renin and Aldosterone Biosynthesis in the Adrenal Cortex by Angiotensin II AT₁-Subtype Receptors

Bruna Gigante; Speranza Rubattu; Rosaria Russo; Antonio Porcellini; Iolanda Enea; Paola De Paolis; Carmine Savoia; Armando Natale; Ornella Piras; Massimo Volpe

From the Department of Internal Medicine "Federico II" University Naples (B.G., R.R., C.S., A.N., O.P.), the IRCCS Istituto Neurologico Mediterraneo "Neuromed" Pozzilli (Is) (S.R., A.P., I.E., P. De P., M.V.), and the Department of Experimental Medicine and Pathology "La Sapienza University" (M.V.), Rome, Italy.

Correspondence to Massimo Volpe, MD, Istituto Neurologico Mediterraneo "Neuromed," Via Atinense 18, Località Camerelle, 86077 Pozzilli (Is), Italy. E-mail volpema{at}cds.unina.it

Abstract The aims of this study were to identify whether tissue renin is regulated by a negative-feedback mechanism produced by locally generated angiotensin (Ang II) in the adrenal cortex and to detect the pathway of Ang II modulation. For this purpose, in 36 12-week old, salt-restricted, nephrectomized Sprague-Dawley rats, we studied the effects of the Ang II AT₁-subtype receptor antagonist losartan and of the Ang II AT₂-subtype receptor antagonist PD123319 on renin mRNA and activity, aldosterone synthase mRNA, and AT_1a-, AT_1b-, and AT₂-subtype receptor expression in the adrenal cortex. Ten additional rats, kept on a regular diet and then nephrectomized, were also studied. In salt-restricted, 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 losartan AT_1b, receptor mRNA was reduced (P<.05), AT_1a receptor mRNA was unchanged, and AT₂ mRNA was increased (P<.05). PD123319 did not significantly modify any of these parameters. In conclusion, in salt-restricted, nephrectomized rats, selective antagonism of AT₁-subtype 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 action 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.

Key Words: aldosterone • adrenal • renin • angiotensin II • receptors

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