Does chlorothiazide lower blood pressure through plasma and extracellular fluid volume depletion?
The early antihypertensive effect of chlorothiazide is driven by volume depletion, but its long-term efficacy at 1 year is mediated by other mechanisms as extracellular fluid reaccumulates.
The importance of plasma and extracellular fluid volumes in the mechanism of the antihypertensive effect of chlorothiazide is disputed. The present investigation indicates that the lowering of blood pressure is accompanied by reductions in plasma and extracellular fluid volumes and in body weight. Furthermore, re-expansion of plasma volume with salt-free dextran reverses the antihypertensive effect. However, since gradual reaccumulation of extracellular fluid occurs during 1 year of continuous treatment, the late antihypertensive effects of chlorothiazide cannot be explained by the volume-depletion mechanism.
Wilson et al. (Tue,) studied this question.