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 < or =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<0.001) and 4.6+/-1.6 (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.