The Antihypertensive Mechanisms of Salt Depletion Induced by Hydrochlorothiazide

Abstract

Hydro-chlorothiazide reduced significantly basal systolic and diastolic pressures and levels of blood pressure during infusions of norepinephrine in 10 hypertensive subjects. The diuretic increased depressor responses to trimethapan and erythrol tetranitrate. Re-expansion of plasma volume by Dextran lessened the effects of hydrochlorothiazide on basal systolic pressure and systolic responses to trimethapan and erythrol tetranitrate, but did not reverse the effects of the diuretic on basal diastolic pressure, systolic responses to norepinephrine or protoveratrine B, or diastolic responses to the 4 vasoactive substances studied. Addition of 20 g of salt daily returned all blood pressure responses approximately to control levels. Two indirect studies suggest that arteriolar contractility is not impaired by the degree of salt depletion induced by hydrochlorothiazide. The relative increments of response to norepinephrine were not decreased by the diuretic. After reexpansion of plasma volume by Dextran and the addition of an intravenous infusion of angiotensin II at a rate determined to return systolic and diastolic pressures to pre-diuretic levels during continued administration of hydrochlorothiazide, the response to norepinephrine was similar to that before the diuretic was administered. It is concluded that the antihypertensive effects of hydrochlorothiazide are related to salt depletion, which acts by an effect of oligemia on systolic pressure and by an additional mechanism that decreases peripheral vascular resistance. The latter appears due to a reduction in the degree of humoral or neurogenic vasoconstrictor stimulation of the arteriolar bed.