Clinical Evaluation of Diazoxide: a New Treatment for Acute Hypertension.

THE effectiveness of ehlorothiazide and related compounds as diuretics and antihypertensive agents has been well established. Much confusion still exists, however, regarding the exact mechanisms by which these ag,ents reduce arterial pressure. Although it has not been fully established whether the reduction in arterial pressure following the thiazides is due solely to sodium diuresis,1 is secondary to a decrease in plasma volume,2 or is the result of removal of sodium or water from the blood vessels, the hypotensive effect seemed3 at least in some way related to sodium diuresis. It is understandable, therefore, that the synthesis of a compound that reduces arterial pressure but causes sodium retention would create much interest. Diazoxide is structurally similar to chlorothiazide (fig. 1). Rubin, Roth, and Winbury4 suggested either that this agent might represent a true separation of the antihypertensive properties associated with the benzothiazine diuretics or that it nlight be representative of a new class of antihypertensive agents. Studies from this laboratory with a very alkaline solution of diazoxide have shown that it is a potent antihypertensive agent in man.5 A 300-mg. dose administered slowly in two or three divided doses intravenously caused a prompt reduction in arterial pressure, which was associated with an increase in the cardiac output and a decrease in total peripheral resistance. The reduction in arterial pressure