The Effects of Angiotensin II Blockade in Conscious Sodium-Depleted Dogs*

Abstract

The role of the renin-angiotensin system in the control of the plasma aldosterone concentration was examined during both acute (n = 5) and chronic sodium depletion (n = 12) in conscious dogs. A striking increase in the plasma aldosterone level occurred following ethacrynic acid administration alone but the response was completely blocked by simultaneous infusion of [Sar1, Ala8]- angiotensin II. Plasma renin activity (PRA) increased further and arterial pressure fell during the combination of ethacrynic acid injection and angiotensin analogue infusion. The data are explicable on the basis of angiotensin II as die primary and sole mechanism responsible for the increased plasma aldosterone level. In dogs with chronic sodium depletion, both [Sar1, Ala8]-angiotensin II and the converting enzyme inhibitor SQ 20881 produced a striking fall in the plasma aldosterone concentration and arterial pressure and an increase in PRA; the responses were qualitatively identical for the two blocking agents. Failure of the plasma level of aldosterone to fall to the normal level with both agents probably reflects the presence of zona glomerulosa hypertrophy. Administration of [des-Asp1, Ile8[angiotensin II to chronic, sodiumdepleted dogs failed to decrease plasma aldosterone; instead, apparently an agonistic response in aldosterone occurred. The present observations indicate that the renin-angiotensin system is the sole mechanism for the control of aldosterone secretion in the dog during acute sodium depletion and that it plays a primary essential role during chronic sodium depletion.