An investigation into the effects of nifedipine and nimodipine on platelet function and vascular prostacyclin synthesis.

The effect of two calcium-channel blockers (nifedipine; nimodipine) on in vitro platelet function and prostacyclin (PGI2) synthesis was investigated. Platelet aggregation and thromboxane A2 release in platelet-rich plasma were inhibited by both drugs, but the effective concentrations (20 mg/l) were considerably higher than the reported therapeutic levels of the drugs (60 micrograms/l). Platelet impedance aggregometry (PIA) in whole blood was a more sensitive (4-fold) index of the effect of nifedipine on platelets, but inhibitory concentrations of the drug were still considerably higher (5 mg/l) than therapeutic concentrations. Neither nifedipine nor nimodipine had any effect on PGI2 synthesis, which was assessed in terms of conversion of arachidonic acid to PGI2 (in rat aortic and human umbilical tissue) and spontaneous release of PGI2 from rat aortae following in vitro incubations or in vivo administration of nifedipine. The mechanism responsible for the reported inhibition of platelet function following administration of nifedipine remains unclear, but does not appear to involve acute direct effects on platelets or vascular PGI2 production. The authors' PIA findings also indicate that: (a) PIA may be a more sensitive method than conventional (PRP) aggregometry to demonstrate platelet antiaggregatory effects of drugs; and (b) erythrocytes and leucocytes may be involved in the mechanism underlying the antiaggregatory effect of nifedipine.