Deferential roles of angiotensin receptor subtypes in adrenocortical function in mice

The functional significance of angiotensin II (Ang II) receptor subtypes in adrenals remains unknown. Ang II receptor type 1a (AT1a) expression was localized by in situ hybridization to the zona glomerulosa and zona fasciculata, while AT1b was localized to the zona glomerulosa. Plasma aldosterone and corticosterone levels were measured after injection with Ang II or the type 2 receptor (AT2) agonist CGP-42112 in wild-type and AT1a deficient mice. Aldosterone and corticosterone levels were lower in AT1a deficient mice. Ang II increased plasma aldosterone levels in AT1a deficient mice, but to a lesser extent in mice pretreated with nonselective AT1a/AT1b antagonist, CV-11974. CGP-42112 did not affect aldosterone levels. Ang II increased corticosterone levels in wild-type mice but not in AT1a deficient mice. Results suggest Ang II stimulates aldosterone secretion via AT1a and AT1b in the zona glomerulosa and corticosterone secretion via AT1a in the zona fasciculata, and provide first evidence for differential roles of AT1a and AT1b in the adrenals.