Adrenocorticotropin-mediated effect of metoclopramide on plasma aldosterone in man

Five healthy adult men were given metoclopramide (10 and 20 mg) iv and the effects of L-dopa and dexamethasone on metoclopramide-induced increases in plasma aldosterone concentration were determined. Plasma PRL, ACTH, and cortisol levels were also measured and the results reported in a previous study. After an injection of 10 mg metoclopramide, aldosterone levels increased significantly. The aldosterone rise was inhibited by L-dopa, but not by dexamethasone. After injecting 20 mg metoclopramide, aldosterone levels increased significantly vs. both the control and the basal level. The aldosterone increase was not inhibited by L-dopa pretreatment, whereas pretreatment with dexamethasone did suppress it. The data suggest that metoclopramide increased aldosterone secretion through an ACTH-dependent (stress mediated) effect in addition to its antidopaminergic adrenal action, simultaneously. There were no significant differences between the ACTH-dependent and dopamine antagonist-mediated aldosterone increases in either the 10- or 20-mg tests. However, the ACTH-dependent aldosterone increase was statistically greater in the 20-mg test than in the 10-mg test, whereas there was only a slight and not statistically significant difference in the dopamine antagonist-mediated aldosterone increase between the tests. This means that the ACTH-dependent component of the aldosterone secretion is affected by the doubling of the metoclopramide dose, whereas the dopamine antagonist-mediated component is not.