THE CALCIUM MODULATOR NIFEDIPINE EXERTS ITS ANTIAGGREGATORY PROPERTY VIA A NITRIC-OXIDE MEDIATED PROCESS

The in vitro effect of nifedipine, a calcium channel blocker of the di hydropyridine (DHP) type, on platelet aggregation was reinvestigated c onsidering especially the capability of platelets to form endogenous n itric oxide (NO). We studied the dose-dependent antiaggregatory proper ty of nifedipine in porcine platelet rich plasma. Aggregation was stim ulated by collagen (7.5 mu g/ml). Nifedipine inhibited collagen-induce d platelet aggregation with an IC50 of 380 nmol/l. The antiaggregatory effect of nifedipine could be significantly diminished by N-nitro-L-a rginine (NNA) in a concentration dependent manner, whereas oxy haemogl obin (4 mu M), a NO scavenger, totally abolished the effect of nifedip ine. L-Arginine, the precursor of NO, dose-dependently inhibited the c ollagen-induced platelet aggregation but did not potentiate the effect s of nifedipine. Therefore, we propose that in platelet rich plasma th e nifedipine induced inhibition of platelet aggregation is mediated by NO, a potent endogenous inhibitor of aggregation. We could confirm th is hypothesis by measuring NO directly with a specific electrode.