Regulation of growth of the adrenal gland in DOC-salt hypertension - Role of angiotensin II receptor subtypes

To investigate the role of the renin-angiotensin system in the regulation of adrenal growth in deoxycorticosterone (DOC)-salt hypertensive rats, and the adrenal gene expression of angiotensin AT(1) and AT(2) receptors, three groups of uninephrectomized rats+DOC pellet+0.9% NaCl were given water (DOC), losartan (DOC-L), or ramipril (DOC-R) by gavage. Controls had sham surgery and water gavage. Tail-cuff systolic and mean intra-arterial blood pressures were significantly higher in the three DOC groups than in controls and not different among the groups. Adrenal weight of DOC was slightly but not significantly greater than that of controls, while those of DOC-L and DOC-R were greater than that of controls (P<.01). Northern blots showed that AT(1) and AT(2) gene expression was significantly reduced in DOC (by 33% and 60%), while that of AT(1) (but not AT(2)) was significantly reduced further (versus control and DOC) in DOC-L and DOC-R. There were negative correlations between adrenal weight and AT(1) (r = -.80, P < .0001) or AT(2) (r = -.60, P < .005). We conclude that DOC-salt hypertension downregulates adrenal AT(1) and AT(2) gene expression by different mechanisms. Removal of the effects of angiotensin by losartan or ramipril downregulates AT(1) further and promotes adrenal growth, indicating the presence of an AT(1)-mediated growth-inhibitory action of angiotensin II on the adrenal gland. These observations constitute an additional example of a growth-inhibitory role for the AT(1) receptor, opposite to its more common growth-promoting actions in other organs and tissues.