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Possible Mechanism of Action of Metoclopramide-Induced Aldosterone Secretion: In Vivo and in Vitro Studies in the Sheep^*

THOMAS A. WILSON, DONALD L. KAISER, MICHAEL J. PEACH, EUGENE M. WRIGHT and ROBERT M. CAREY

Division of Endocrinology and Metabolism, Department of Internal Medicine, and the Departments of Pediatrics, Pharmacology and Comparative Medicine, University of Virginia School of Medicine Charbttesville, Virginia 22908

Address requests for reprints to: Dr. Robert M. Carey, Division of Endocrinology and Metabolism, Department of Internal Medicine, Box 482, University of Virginia School of Medicine, Charlottesville, Virginia 22908.

Abstract

To define further the mechanism by which metoclopramide, a dopamine antagonist, stimulates aldosterone secretion, seven lambs were injected iv 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, potassium, and angiotensin II, but no increase in aldosterone concentration occurred in the presence of metoclopramide.

These results suggest that 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. (Endocrinology 113: 887,1983)

Footnotes

^* This work was supported by Hypertensin Research Training Grant HL-07355 and in part by Research Grant HL-22306 from the NIH.

Current address: Department of Pediatrics, T-ll Health Sciences Center, State University of New York, Stony Brook, New York 11794.

Received August 13, 1982.