Prolonged inhibitory effects of nilvadipine (FR34235) following washout in isolated rabbit aorta and mesenteric artery.

Duration of the inhibitory effects of nilvadipine and some other Ca2+ entry blockers following washout was studied in isolated rabbit aorta and distal portion of mesenteric artery. The inhibitory effects of nilvadipine on KCl-induced contraction of aorta lasted longer than those of diltiazem, nifedipine, and nicardipine. Durations of nilvadipine were dose-dependently prolonged. The 50% recovery time, a parameter of the duration of action following washout, of nilvadipine at 10(-9) and 3 X 10(-9) M was 2.5 and 3.2 h, respectively. The long-lasting inhibitory effects of nilvadipine were pronounced at low [Ca]o. Similar prolonged actions of nilvadipine, compared with those of diltiazem and nifedipine, were observed in norepinephrine (NE)-induced contraction of the distal portion of mesenteric artery, of which tonic contractions were highly sensitive to Ca2+ entry blockers. Despite the long action of nilvadipine after washout in mesenteric artery, the onset of the inhibition of NE contraction was prompt. These pharmacological properties of nilvadipine, especially those seen in mesenteric artery, may be consistent with its long action as an antihypertensive agent.