Spironolactone and amiloride in hypertensive patients with and without aldosterone excess

The antihypertensive action of spironolactone has been ascribed to both a nonspecific diuretic and a specific antimineralocorticoid effect. To better evaluate the relative importance of these effects, we compared its effects with the mineralocorticoid-independent drug amiloride. Spironolactone (400 mg/day) and amiloride (40 mg/day) were given to 10 patients with essential hypertension (EH) and to 10 patients with hypertension and supranormal aldosterone secretion (SNA). After 6 wk, blood pressure responded better to spironolactone (−20.5%) than to amiloride (− 10.4%) in patients with SNA, but the response was similar in patients with EH (−7.4% and −6.5%). The decrease in body weight—as a measure of volume depletion—was greater after spironolactone (−4.6%) than after amiloride both in patients with SNA (−4.6% and −0.8%) and in patients with EH (−3.7% and −0.6%). After both drugs, plasma sodium decreased (−3.4% and −2.6%) and plasma potassium increased (+37.2% and +32.6%) to the same extent in patients with SNA, reflecting a similar degree of antimineralocorticoid-like activity. After spironolactone patients with SNA showed a greater rise in PRA than after amiloride (412% and 82%). Despite the greater rise in PRA, the rise in aldosterone excretion was in the same range after both drugs (113% and 195%), pointing to inappropriately low aldosterone excretion after treatment with spironolactone. We conclude that differences in volume depletion or antimineralocorticoid-like activity cannot explain the better response in blood pressure of patients with SNA after spironolactone than after amiloride. Our data provide evidence for a specific antialdosterone effect of spironolactone in lowering the blood pressure, especially in patients with aldosterone excess. Clinical Pharmacology and Therapeutics (1980) 27, 317–323; doi:10.1038/clpt.1980.42