On the Mechanism of Antihypertensive Action of Hydrochlorothiazide in Rats

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Abstract
Hydrochlorothiazide significantly diminishes blood pressure in rats with DCA hypertension. Infusion with hypertonic saline or dextrose failed to reverse the blood pressure effects of hydrochlorothiazide. Infusion of hypotonic saline failed to restore blood pressure to the levels of hypertension in untreated controls in one experiment but tended to do so in another. There was no significant diminution of the inulin space accompanying the hypotensive action of hydrochlorothiazide, nor any relation between the expansion of the extracellular and cardiovascular volumes by various infusions and their effects on blood pressures of thiazide-treated rats. Plasma or extracellular fluid volume alteration was, therefore, not the primary action of hydrochlorothiazide in these rats. Analyses of the composition of plasma, aorta, stomach muscle, psoas muscle, or left ventricle did not support the theory that hydrochlorothiazide acts by decreasing the concentration of intracellular sodium or increasing the ratio of extracellular to intracellular sodium. Changes in composition of the left ventricle suggested that alterations in its function may have influenced some of the blood pressure changes noted. It is suggested that attention should be paid to the action of hydrochlorothiazide on other constituents in vascular and cardiac muscle.