Rapid development of tolerance to the antihypertensive effect of nisoldipine

Antihypertensive efficacy and tolerability of the dihydropyridine calcium antagonist nisoldipine were examined in a double-blind, placebo-controlled study. Twenty patients with hypertension (greater than 140/95 mmHg) uncontrolled by bendrofluazide plus atenolol were randomly allocated to receive nisoldipine, 10-20 mg daily, or placebo for six weeks. Nisoldipine, compared with placebo, lowered blood pressure (BP) by 31/21 mmHg (P less than 0.02/P less than 0.002) after two weeks. Thereafter its antihypertensive effect declined to 20/9 mmHg (NS/NS) at four weeks and 8/3 mmHg at six weeks (NS/NS). Compared with placebo, the rise in BP with nisoldipine during the last four weeks of the trial was highly significant (P less than 0.005). During this period BP rose by 14/11 mmHg (P less than 0.05/P less than 0.02) in the nisoldipine group so the apparent loss of effect was not attributable to a fall of BP in the placebo group. Compliance, as assessed by tablet counts, was satisfactory and nisoldipine treatment did not cause significant weight gain. The drug was not well tolerated and three patients withdrew from treatment because of side-effects. Tolerance to the antihypertensive effect of nisoldipine appears to develop rapidly and further studies should be performed to confirm this, and evaluate the mechanism.