Diuretics and blood pressure reduction: physiologic aspects.

Among the many classes of diuretics available, thiazides have emerged as the most appropriate category for the treatment of uncomplicated hypertension. Potassium-sparing agents may be added according to need or in fixed-combination therapy. Thiazides act on the cortical diluting segment of the renal tubule. The potassium-sparing agents interfere with the Na(+)-K+ exchange process in the terminal part of the distal tubule. Thiazides have been the cornerstone of therapy in nearly all prospective therapeutic, mild and moderate hypertension trials conducted to date. They have, therefore, proved their value in the prevention of hypertensive cardiovascular complications such as stroke and congestive heart failure. The physiologic changes occurring during antihypertensive treatment with thiazides have been extensively studied. The initial response to a thiazide is characterized by a mildly negative change in sodium and fluid balance. The resulting slight contraction in plasma volume is followed by reductions in cardiac output and blood pressure. Because these reductions are disproportionate, vascular resistance rises initially. In the longer term, plasma volume is partly restored, and cardiac output re-attains the baseline level. Thus, the reduction in blood pressure ultimately appears to be based on vasodilation. The mechanisms of this biphasic vascular response are not completely understood. This lack of insight, however, does not detract from the proven value of thiazides in treating hypertensive subjects.