Mechanism of antihypertensive effect of thiazide diuretics

Hemodynamic studies were carried out before and during 8 weeks of treatment with hydrochlorothiazide 50 mg. twice daily in 11 hypertensive patients. Forty-eight hours after beginning treatment there was a significant reduction in blood pressure, cardiac output, plasma volume, and extracellular fluid volume (thiocyanate space) while total peripheral resistance increased. After 6 and 8 weeks of treatment, the blood pressure and the plasma and extracellular volumes remained reduced. However, total peripheral resistance fell while cardiac output rose to control levels. These results were consistent with the "reverse autoregulation" theory of the action of the thiazides as proposed by Tobian. The present evidence discussed below makes it appear unlikely that the thiazides have an important direct vasodilator effect.