Vasoconstrictor expression of human platelet-vessel wall interactions: inhibition by the Ca2+ entry blocker...

Human blood platelets, stimulated with thrombin, induced contractions of isolated basilar artery segments of the dog. These platelet-mediated vascular contractions were inhibited in a concentration-dependent way by flunarizine, a Ca2+ entry blocker, selective for vascular tissues (IC50: 5.5 X 10(-7) M). This inhibition increased gradually as a function of the time contact with flunarizine, to reach its maximum after 60-90 min. Biochemical and pharmacological analyses using the S2-serotonin receptor antagonist ritanserin, the thromboxane A2/prostaglandin endoperoxide antagonist BM 13.177 and the fatty acid cyclo-oxygenase inhibitor suprofen showed that 5-hydroxytryptamine and prostanoids (thromboxane A2, prostaglandin endoperoxides) were the main mediators involved. The results further suggested amplification between the vascular effects of 5-hydroxytryptamine and prostanoids. Flunarizine did not affect the release of 5-hydroxytryptamine from platelets and did not interfere with their biosynthesis of thromboxane A2.