The Renin-Angiotensin System and Aldosterone Secretion during Sodium Depletion in the Rat

Abstract

The role of the renin-angiotensin system in the control of aldosterone secretion was studied in the sodium-depleted rat. Administration of angiotensin II produced a significant increase in aldosterone secretion and arterial blood pressure in normal rats; simultaneous infusion of the angiotensin analogue. 1-sarcosine-8-alanine-angiotensin II, blocked both the pressor and the steroidogenic actions of angiotensin. Since the angiotensin II analogue was effective in blocking exogenous angiotensin II, an attempt was made to block endogenously formed angiotensin II in the sodium-depleted rat; infusions of large doses of the analogue produced a significant fall in arterial blood pressure, but aldosterone secretion failed to change. Bilateral nephrectomy also failed to decrease aldosterone secretion in the sodium-depleted rat even though arterial blood pressure fell. Since the secretion of corticosterone in these rats was high, it seemed likely that the failure of aldosterone secretion to fall resulted from an overriding influence of adrenocorticotropic hormone (ACTH). To test this hypothesis, the renin-angiotensin system was again blocked in sodium-depleted rats with three levels of anterior pituitary function. With high or intermediate rates of corticosterone secretion, a nonapeptide converting enzyme inhibitor (CEI) failed to influence aldosterone secretion. However, when the influence of ACTH was completely eliminated by hypophysectomy in sodium-depleted rats, the nonapeptide CEI produced a striking fall in aldosterone secretion. In contrast, arterial blood pressure was significantly reduced by CEI in rats with all three levels of anterior pituitary function. The data suggest a role for angiotensin II in the regulation of aldosterone secretion and the maintenance of arterial blood pressure in the sodium-depleted rat.