Treatment of arterial hypertensive disease with diuretics. V. Spironolactone, an aldosterone antagonist

Abstract

Fifty patients with benign essential hypertension received 600 mg daily of spironolactone (equivalent to 150 mg daily of spironolactone) for 3 mo. in a paired double-blind study. The resultant modest but highly significant (P < 0. 001) lowering of mean blood pressure of 7. 1% was well tolerated by all patients. One fifth of patients with milder hypertension experienced a reduction of blood pressure to normal values. The antihypertensive response to spironolactone was distinctly less than that obtained with bendroflumethiazide or chlorthalidone. The antihypertensive response of individual patients to spironolactone was totally unrelated to that of bendroflumethiazide of chlorthalidone. This suggests a different mechanism of antihypertensive drug action. Changes in serum electrolytes and urea induced by spironolactone were minimal and clinically unimportant in nonuremic patients. Nine patients with preexistent mild azotemia experienced a slight rise of blood urea nitrogen (BUN); two of these patients also had rises of serum potassium to 6. 2 and 6. 3 mEq/liter. Severe hyperkalemia may develop in patients with more advanced uremia. The mean percentage reduction of blood pressure from spironolactone was normally distributed. Statistical analyses failed to uncover a subgroup of patients with characteristics suggestive of primary hyperaldosteronism. Various correlations of responses of blood pressure and serum K and HCO3 measured while receiving spironolactone, thiazide, or chlorthalidone were sought, but a statistically separate population could not be demarcated. This study failed to find evidence in support of aldosteronism as a primary cause for the maintenance of excessive blood pressure in a substantial number of patients with essential hypertension.