Possible Mechanism of Action of Metoclopramide-Induced Aldosterone Secretion:In Vivoandin VitroStudies in the Sheep*

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Abstract
To define further the mechanism by which metoclopramide, a dopamine antagonist, stimulates aldosterone secretion, 7 lambs were injected i.v. with metoclopramide during a constant infusion of 5% dextrose in water and again during a constant infusion of trimethapan, a ganglionic blocker. In addition, suspensions of adrenal zona glomerulosa cells from the lambs were incubated in vitro in the presence of various concentrations of metoclopramide and known secretagogues. Plasma aldosterone concentrations increased in response to both metoclopramide and trimethaphan. However, during the trimethaphan infusion, no further increase in plasma aldosterone concentrations occurred after metaclopramide injection. In vitro aldosterone concentrations in the zona glomerulosa cell suspensions increased in the presence of ACTH, K and angiotensin II, but no increase in aldosterone concentration occurred in the presence of metoclopramide. Apparently in the sheep, metoclopramide stimulates aldosterone secretion by an indirect mechanism. This mechanism may involve the autonomic nervous system, since ganglionic blockade appeared to abolish the aldosterone response to metoclopramide.