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 dihydropyridine (DHP) type, on platelet aggregation was reinvestigated considering especially the capability of platelets to form endogenous nitric oxide (NO). We studied the dose-dependent antiaggregatory property of nifedipine in porcine platelet rich plasma. Aggregation was stimulated by collagen (7.5 micrograms/ml). Nifedipine inhibited collagen-induced platelet aggregation with an IC50 of 380 nmol/l. The antiaggregatory effect of nifedipine could be significantly diminished by N-nitro-L-arginine (NNA) in a concentration dependent manner, whereas oxy haemoglobin (4 microM), a NO scavenger, totally abolished the effect of nifedipine. L-Arginine, the precursor of NO, dose-dependently inhibited the collagen-induced platelet aggregation but did not potentiate the effects of nifedipine. Therefore, we propose that in platelet rich plasma the nifedipine induced inhibition of platelet aggregation is mediated by NO, a potent endogenous inhibitor of aggregation. We could confirm this hypothesis by measuring NO directly with a specific electrode.
Berkels
R
R
Institut für Pharmakologie, Universität zu Köln, Germany.
Klaus
W
W
Boller
M
M
Rösen
R
R
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D009543:Nifedipine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood / Q000502:physiology*; D019335:Nitroarginine; D010108:Oxyhemoglobins / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013552:Swine
D010108:Oxyhemoglobins; D010975:Platelet Aggregation Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D009543:Nifedipine