The Antihypertensive Actions of Benzothiadiazines

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Abstract
Blood pressure, body weight, extracellular fluid and plasma volumes, 24-hour exchangeable Na and K, and serum K were reduced after 6 to 8 weeks of administration of chlorothiazide in 20 nonedematous hypertensive subjects. The loss of weight, water, and Na approximated the loss of a liter of isotonic extracellular fluid. Addition of 20 g of salt daily during benzothiadiazine administration in 10 patients returned body weight and blood pressure to pretreatment levels, but further lowered 24-hour exchangeable K. The addition of 8 g of salt daily usually failed to restore body weight to control levels and did not oppose the antihypertensive effects of chlorothiazide. Expansion of plasma volume by Dextran to levels slightly above pretreatment values was associated with a rise in systolic blood pressure but not to control levels and no significant change in diastolic levels in 10 patients during benzothiadiazine administration. The antihypertensive effects of benzothiadiazines are due to Na depletion and are not related to K loss. At least 2 mechanisms of antihypertensive action must be involved, one related to the effects of oligemia, and another possibly to an impairment of the function of a humoral or neurogenic pressor system.