Improvement in Blood Pressure With Inhibition of the Epithelial Sodium Channel in Blacks With Hypertension

Abstract

Hypertension in blacks is more prevalent and less often controlled than the hypertension of other ethnic groups. We sought to explore the benefit of adding inhibitors of the epithelial sodium channel (ENaC), an aldosterone-regulated site of sodium reabsorption in the distal nephron, to the antihypertensive regimen of black hypertensive patients. In a prospective, randomized, placebo-controlled, double-blind clinical trial, we used a 2-by-2 factorial design with 4 treatment groups: amiloride (a direct inhibitor of ENaC), spironolactone (an aldosterone receptor antagonist), the combination of both drugs, and placebo. The subjects (n=98) had an elevated blood pressure despite treatment that included a diuretic and a calcium channel blocker; the level of plasma renin activity was ≤0.56 ng/L per second. The primary end points were changes from baseline in systolic and diastolic blood pressure over a 9-week period of treatment. The reductions in systolic and diastolic blood pressures (mm Hg) were, respectively, 9.8±1.6 (SE) and 3.4±1.0 for amiloride ( P P =0.006) and 1.8±1.0 for spironolactone ( P =0.07). Treatment with either amiloride or spironolactone or the combination was well tolerated; no patient experienced hyperkalemia. In a substudy, plasma endothelin-1 levels were observed to decrease after 3 weeks of treatment with spironolactone ( P <0.001), consistent with a non–ENaC-related potential benefit of spironolactone. In conclusion, treatment with either amiloride or spironolactone can provide an additional reduction in blood pressure in blacks already receiving conventional antihypertensive therapy.