Clinical observations on an antihypertensive chlorothiazide analogue devoid of diuretic activity.

The antihypertensive effect of the diuretic benzothiadiazines has been attributed to salt depletion and the resultant reduction in plasma volume. The study described in this report was concerned with the effects of diazoxide, a non-diuretic analogue which had been found in animal experiments to have a hypotensive effect.Intravenous diazoxide (3 mg./kg.) reduced blood pressure an average of 26/16 mm. Hg in seven hypertensive subjects. An associated rise in cardiac output (0.7 to 5.7 1./min.) and decrease in peripheral vascular resistance occurred. There was no postural hypotension, or change in external salt balance or in the concentration of serum sodium or potassium.Oral administration of the drug (0.2 to 0.5 g./day for eight to 50 weeks) lowered blood pressure more than 15/10 mm. Hg in 26 of 30 hypertensive subjects. Associated effects were: (1) weight gain in 26 of 30 subjects, (2) anorexia in 15 of 30, (3) lacrimation in six of 30, (4) aggravation of diabetes in two, and (5) transient cardiac arrhythmias in four. This study suggests that this benzothiadiazine acts directly on arterioles to reduce peripheral vascular resistance.