Regulatory Actions of Angiotensin II on Receptors and Steroidogenic Enzymes in Adrenal Glomerulosa Cells

Abstract

The trophic effects of angiotensin II (AII) on adrenal glomerulosa function were studied by prolonged infusion of the Ile⁵-octapeptide in intact and 14-day hypophysectomized rats. The administration of a nonnatriuretic dose of AII (50 ng/ min) for 6 days elevated blood levels of AII 3-fold and increased the plasma aldosterone concentration from 9.6 ± 1.2 to 29.7 ± 5.7 ng/dl in intact rats and from 7.5 ± 1.5 to 31.6 ± 7.4 ng/dl in hypophysectomized rats. AII receptors measured in adrenal glomerulosa fractions from hypophysectomized rats were increased 2-fold, from 1408 ± 138 to 2270 ± 324 fmol/mg. Significant increases in enzymes of the aldosterone biosynthetic pathway, more marked in hypophysectomized animals, were observed after AII infusion. Mitochondrial cholesterol content and pregnenolone formation were increased by 30% in intact rats and by 100% and 240%, respectively, in hypophysectomized rats. The conversion of corticosterone to aldosterone was also increased, by 100% in intact rats and by 180% in hypophysectomized rats. Microsomal cytochrome P-450 and 21-hydroxylase activities did not change after AII infusion in intact rats but were increased by about 100% in hypophysectomized rats. There was also an increase of 35% in 11-hydroxylase activity in hypophysectomized rats after AII infusion. These data show that the trophic actions of AII on the adrenal glomerulosa zone are manifested by increases in both AII receptors and enzymes of the steroid biosynthetic pathway. The stimulatory effects of AII on 21-hydroxylase and 11-hydroxylase were most obvious in hypophysectomized rats, when basal levels of the enzymes were decreased in the absence of ACTH. These studies demonstrate that AII infusion reproduces the effects of sodium restriction on the glomerulosa cell and confirm the importance of AII as the major regulator of adrenal function during altered sodium intake.