Dopaminergic Modulation of Aldosterone Secretion in Man is Unaffected by Glucocorticoids and Angiotensin Blockade

This study examines the mechanism of dopaminergic modulation of aldosterone secretion in normal man. Nine normal male volunteers in metabolic balance at 100 meq sodium/ day and 60 meq potassium/day constant intake received metoclopramide (10 mg iv) with 5% dextrose (vehicle), with dopamine (3 εg/kg-min, with saralasin (10 εg/kg-min), or after 4 days of dexamethasone (2 mg orally every 6 h) or placebo. Metoclopramide in the presence of vehicle increased plasma aldosterone concentrations from 12.5 ± 1.2 to a maximum of 25.0 ± 2.5 ng/dl (P < 0.01) and serum PRL concentrations from 10.0 ± 1.1 to a maximum of 74.9 ± 8.6 ng/ml. The aldosterone and PRL responses displayed a parallel time course, with significant responses of both occurring 5 min after metoclopramide administration. A significant rise (P < 0.05) in plasma renin activity (PRA) from 2.7 ± 0.4 ng/ml h−1 to 4.5 ± 1.0 ng/ml h−1 was observed only at the 30-min sampling time. Dopamine infusion suppressed the aldosterone, PRL, and PRA responses to metoclopramide. Saralasin infusion for 60 min before metoclopramide suppressed basal aldosterone (P < 0.05) and markedly elevated (P < 0.001) PRA. However, saralasin did not alter the plasma aldosterone or serum PRL response to metoclopramide. The very high PRA values did not increase further after metoclopramide when the subjects were being infused with saralasin. High dose dexamethasone for 4 days suppressed the serum PRL response but had no effect on aldosterone or PRA responses to metoclopramide. The results of this investigation suggest that aldosterone, PRL, and PRA responses to metoclopramide are mediated by metoclopramide's antagonist activity at the level of central or peripheral dopamine receptors. Metoclopramide stimulation of aldosterone secretion appears to be independent of effects it has on PRL, ACTH, electrolytes, and the renin-angiotensin system.