THE EFFECT OF METOCLOPRAMIDE AND DOPAMINE ON PLASMA-ALDOSTERONE CONCENTRATION IN NORMAL MAN AND RHESUS-MONKEYS (MACACA-MULATTA) - A NEW MODEL TO STUDY DOPAMINE CONTROL OF ALDOSTERONE SECRETION

Metoclopramide, a dopamine receptor antagonist, increases plasma aldosterone concentration in man, suggesting that dopamine regulates the secretion of aldosterone. Metoclopramide was administered to rhesus monkeys and normal subjects and the time-course and dose-response characteristics of plasma aldosterone were compared. The effect of dopamine on the plasma aldosterone response to metoclopramide in both species was also examined. Six male rhesus monkeys and 7 normal subjects (5 women and 2 men) were studied on diets providing an estimated daily Na intake of 70 mg/kg. In both species the peak increase in plasma aldosterone occurred 15 min after metoclopramide was injected. The peak plasma aldosterone value was 3-fold higher than control values. There were no significant changes in PRA [plasma renin activity], cortisol or K, while plasma PRL [prolactin] increased 7-fold in the monkeys and 11-fold in the normal subjects. After 0.04 mg/kg metoclopramide, there was no change in plasma aldosterone concentration in the monkeys, while aldosterone increased significantly (.DELTA. = 3.7 .+-. 0.68 ng/dl) in the human subjects. The half-maximal dose of metoclopramide was also higher in the monkeys than in the normal subjects. A dopamine infusion at 4.0 to 8.0 .mu.g/kg .cntdot. min partially suppressed the plasma aldosterone response to metoclopramide in both the human subjects and the mnkeys. Metoclopramide produces dose-related increases in plasma aldosterone concentration in the nonhuman primate that are similar to those in normal man and that the increases can be inhibited by dopamine. Aldosterone secretion may be under dopamine control and the rhesus monkey should be an excellent model in which to study further the regulation of aldosterone by dopamine.