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Journal of Pharmacology And Experimental Therapeutics, Vol. 158, Issue 3, 531-539, 1967
Copyright © 1967 by American Society for Pharmacology and Experimental Therapeutics

STUDIES ON THE MECHANISM OF ANTIHYPERTENSIVE ACTION OF DIAZOXIDE: IN VITRO VASCULAR PHARMACODYNAMICS

Arnold J. Wohl 1, Lorraine M. Hausler 1, and Franklin E. Roth 1

1 Department of Pharmacology, Schering Corporation, Bloomfield, New Jersey

Diazoxide (7-chloro-3-methyl-2H-1 ,2,4-benzothiacliazine-1 , 1-dioxide), a nondiuretic benzothiadiazine antihypertensive agent, attenuates vascular responses to a variety of vasoconstrictor substances. An in vitro pharmacodynamic study was designed to specify the type or types of inhibition involved in this vascular action. The results indicate that diazoxide competes with barium for a specific receptor site in the vascular smooth muscle of the rat aorta. The location of this receptor is apparently closer to the process of muscle contraction than the alpha-adrenergic receptor, and may be a site normally activated by calcium. The specific competitive inhibition of barium-stimulated vasoconstriction by diazoxide may help to explain the mechanism by which diazoxide, and possibly other benzothiadiazine antihypertensive agents (e.g., chlorothiazide), reduces blood pressure.

Submitted on March 20, 1967
Accepted on August 18, 1967




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Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics.