Synergistic effect of captopril with hydrochlorothiazide for the treatment of low-renin hypertensive black patients

Diuretics have been particularly successful for treatment of low-renin hypertension (LRH), although they may cause metabolic complications such as hypokalemia and hyperglycemia. Since the efficacy of diuretics is largely limited by reactive angiotensin II production, a combination of a converting enzyme inhibitor with a diuretic should be synergistic, particularly in LRH, where heightened aldosterone production in response to angiotensin II has been noted. Eighteen patients with LRH were treated initially with either captopril alone (450 mg/day) or hydrochlorothiazide (HCTZ) (up to 100 mg/day). Captopril alone only reduced average placebo standing blood pressure from 151/100 to 146/96 mm Hg. Combination of HCTZ with captopril reduced average standing blood pressure to 111/76 mm Hg at 3 months and 116/81 mm Hg at 1 year while allowing reductions in average captopril dosage to 100 mg/day and HCTZ-induced hyperglycemia. Captopril monotherapy did not increase urinary excretion of kallikrein, prostaglandin E₂, or 6-keto prostaglandin F(1α), a metabolite of prostacyclin, and did not reduce urinary aldosterone excretion chronically. Thus, a synergism of captopril with HCTZ may be advantageous in certain patients with LRH.