Effect of Physiological Levels of Atrial Natriuretic Peptide on Hormone Secretion: Inhibition of Angiotensin-Induced Aldosterone Secretion and Renin Release in Normal Man*

Abstract
Large doses of atrial natriuretic peptide (ANP) inhibit renin and aldosterone secretion in normal man, but the effect of physiological levels is unknown. We, therefore, studied the effect of a low infusion rate of .alpha.-human ANP (.alpha.hANP; 0.5 .mu.g/min for 180 min) on the plasma corticosteroid response to graded physiological doses of angiotensin II (0.5, 1.0, 2.0, and 4.0 ng/kg .cntdot. min, each for 30 min) and ACTH (6.25, 12.5, 25, and 50 mIU, each for 30 min) in six normal men eating a low salt diet (10 mmol sodium and 100 mmol potassium daily). The angiotensin II and ACTH infusions were given from 0900-1100 h on separate days, during which randomized infusions of placebo or .alpha.hANP were given from 0800-1100 h according to a single blind protocol. Plasma immunoreactive ANP levels were less than 10 pmol/L on the placebo day compared to 30-50 pmol/L during the .alpha.hANP infusions, and were not altered by either ACTH or angiotensin II. Compared with the control observations, there was no significant change in arterial pressure or heart rate during either the .alpha.hANP or angiotensin II infusions. ACTH infusions evoked an incremental response in plasma aldosterone and cortisol, and the dose-response relationship was unaltered by .alpha.hANP. In contrast, while an incremental and significant increase in plasma aldosterone in response to angiotensin II occurred with the placebo infusion, no significant increase occurred in response to angiotensin during the .alpha.hANP infusion. The slope of the angiotensin II/aldosterone regression line was significantly less during all .alpha.hANP infusions compared to that during the placebo infusion (P < 0.02). In addition, on the ACTH infusion day significant suppression of both PRA (P < 0.05) and plasma angiotensin II (P < 0.008) occurred during the .alpha.hANP infusion compared to that during the placebo infusion, whereas PRA was equally suppressed by angiotensin II in the presence or absence of .alpha.hANP. .alpha.hANP also increased urine volume [176 .+-. 31 (.+-.SEM) vs. 113 .+-. 19 mL/mmol creatinine with placebo; P < 0.03] and sodium excretion (2.14 .+-. 0.48 vs. 0.58 .+-. 0.22 mmol/mmol creatinine with placebo; P < 0.004) on the ACTH infusion days. With angiotensin II, urine volume was also significantly increased by .alpha.hANP (150 .+-. 27 vs. 81 .+-. 15 mL/mmol creatinine with placebo; P < 0.03), and urine sodium excretion doubled. These results in salt-depleted normal men indicate that small increments of .alpha.hANP, approximating 30 pmol/L, are diuretic and inhibit both endogenous renin secretion and angiotensin II-induced aldosterone secretion, but not the adlosterone or cortisol response to ACTH. Since these effects occurred at the plasma ANP levels found by us in volume-loaded normal subjects, we conclude that .alpha.hANP has independent physiological actions on the secretion of renin and aldosterone and on salt balance in man.