Mechanisms by which chlorothiazide potentiates the vasodepressor effect of a ganglion blocking agent (trimethaphan)

Abstract

The potentiation of the antihypertensive effect of trimethaphan by chlorothiazide was studied in eight hypertensive and seven normotensive patients. Trimethaphan was administered intravenously before and forty-five to sixty minutes after the intravenous administration of chlorothiazide. Cardiovascular dynamics were measured during each phase. Total plasma and total blood volumes and fluid balances were measured before each injection of trimethaphan. Chlorothiazide potentiated the vasodepressor effect of trimethaphan in four hypertensive and three normotensive patients. The greater decreases in systemic arterial pressure during the final injection of trimethaphan (after chlorothiazide) were due to greater reductions in total peripheral resistance or cardiac output or both. Stroke output and central blood volume tended to parallel the changes in cardiac output. These data indicate that chlorothiazide increases the vasodilating effects of the ganglion blocking drug upon arteriolar and postarteriolar vessels. Significant diureses, negative fluid balances, significant changes in serum electrolytes or selective decreases in plasma volume did not occur within the initial forty-five to sixty minutes after the administration of chlorothiazide and prior to the final injection of trimethaphan. Small degrees of natruresis were found in some subjects in whom urinary electrolyte levels were measured, but the importance of this factor in the potentiation phenomenon is doubtful. The mechanism of this phenomenon remains an important problem in the field of hypertension.