Differential effects of atrial natriuretic factor on angiotensin II- and adrenocorticotropin-stimulated aldosterone secretion.

Abstract

The possible role of atrial natriuretic factor (ANF) in the regulation of adrenal sensitivity to angiotensin II (AII) was investigated in vivo and in vitro by analyzing the characteristics of the inhibitory effect of ANF on aldosterone production stimulated by AII and other stimuli. In isolated adrenal glomerulosa cells, ANF caused a dose-dependent inhibition of basal and stimulated aldosterone production by submaximal concentrations of ACTH, AII, and potassium, with an ED50 of about 1 nM for ANF and complete inhibition with 10 nM ANF. ANF increased the ED50 for ACTH from 14.6 +/- 3.2 to 376 +/- 104 pM with no significant decrease in the maximum aldosterone response. In contrast, ANF inhibited the aldosterone responses to all doses of AII, decreasing maximal aldosterone production by 75%, with a small increase in the ED50 for AII. In conscious rats, ANF infusion (100 ng/min) markedly decreased the plasma aldosterone response to AII infusion (5-10 ng/min). With higher AII doses (50 and 100 ng/min), which increased plasma corticosterone (and presumably ACTH secretion), the inhibitory effect of ANF was less marked. When the rise in ACTH secretion was prevented by dexamethasone treatment, ANF decreased the aldosterone response to 100 ng/min AII by 85%. Similarly, ANF had a minor although significant inhibitory effect on the primary ACTH-mediated increases in plasma aldosterone after stress by immobilization for 15 min. The data demonstrate a prominent inhibitory effect of ANF on AII-stimulated aldosterone production in vivo and in vitro. Since plasma ANF levels are increased during atrial distension, these observations support a regulatory role of ANF in the control of the adrenal sensitivity to AII during alterations of extracellular volume.