Previous studies by us and other investigators have reported that atrial peptides inhibit the stimulation of aldosterone production in vitro by the three major regulators of aldosterone: angiotensin II, ACTH and potassium. We plan to study the mechanism of this inhibition by atrial peptides. Since we have found a significant difference in the dose response curves of ACTH and angiotensin II to inhibition by ANF (higher doses of ACTH overcome the inhibition while higher doses of angiotensin II do not), we will investigate the dose response curves of K and serotonin both of which may stimulate aldosterone through a cyclic AMP mechanism like ACTH, and presumably will have similar dose response curves. Since calcium is involved in the action of all these stimuli, the effect of atrial peptides on calcium metabolism by the zona glomerulosa will be investigated. We will study the effect of atrial peptides in high and low calcium media, on the efflux of 45 Ca from prelabelled cells, on free cytosolic calcium concentrations, and on membrane potential changes induced by potassium. In view of the stimulation of the polyinositide pathway by angiotensin II we will examine the effect of atrial peptides on this pathway. After establishing the physiological levels of rat ANF 1-28 in plasma, we will infuse physiological doses of rat ANF 1-28 into conscious, unrestrained, cannulated rats to determine whether ANF can inhibit basal, ACTH, angiotensin and K stimulated aldosterone responses and whether the dose response curves are similar in vivo as in vitro. Since there is contradictory evidence that ANF inhibits renin release which may lead to lower aldosterone secretion, we will investigate the action of ANF on renin. By using our superfused renal cortical slice method, we will be able to determine if ANF has a direct inhibitory action on both basal and stimulated renin release. We will also investigate the effect of physiological doses of ANF in vivo in conscious, unrestrained rats on the basal plasma renin levels and on the levels in response to isoproterenol, hypotension, furosemide and angiotensin II.
