Metoclopramide Does Not Elevate Aldosterone in the Rat*

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Abstract
The aldosterone response to metoclopramide (MCP), reported in man and sheep, suggests the existence of a novel aldosterone-regulating mechanism. However, the mechanism and site of action of MCP, whether adrenal or extraadrenal, in the stimulation of aldosterone production in vivo remain to be defined. We have investigated the effect of MCP in the rat in vivo on urinary aldosterone excretion, plasma aldosterone, and aldosterone MCR; in addition, we have examined its in vitro effects on steroidogenesis by isolated zona glomerulosa cells. MCP (0.01–100 mg/kg), given by ip injection to conscious rats, was without effect on urinary aldosterone excretion, despite an 8- to 10-fold response to potassium. Furthermore, other dopamine antagonists (sulpiride, pimozide, domperidone, haloperidol, and chlorpromazine) did not influence urinary aldosterone excretion. MCP (200 μg/kg), given by intraarterial injection to conscious unrestrained chronically cannulated rats, did not affect plasma aldosterone, corticosterone, or renin activity when measured 10–15 min post injection, despite a 3- to 4-fold increase in plasma PRL. Furthermore, MCP was without effect on the plasma clearance of [3H]aldosterone. Studies in vitro revealed that MCP (10-10-10-5, M) had little effect on basal aldosterone production and did not affect potassium-, angiotensin II-, or ACTH-stimulated aldosterone production. Higher concentrations of MCP (10-4-10-3 M) caused nonspecific inhibition of both basal and stimulated aldosterone production. In contrast, MCP (10-6-10-5 M) produced a dosedependent parallel shift to the right of the aldosterone doseresponse curve in response to serotonin. These data demonstrate that MCP does not stimulate aldosterone production in the rat, either in vivo or in vitro. This failure of MCP to elevate aldosterone in vivo may be related to its serotonin antagonist properties.