Thrombin-induced endothelium-dependent inhibition and direct activation of platelet-vessel wall interaction: Role of prostacyclin, nitric oxide, and thromboxane A2

Abstract

Background: Platelet-vessel wall interaction plays an important role in acute cardiovascular disorders. Thrombin is a potent platelet activator but also has profound effects on the endothelium. Endothelial cells possess antithrombotic activity by releasing nitric oxide and prostacyclin, both potent vasodilators and platelet inhibitors. We studied the role of thrombin as a regulator of platelet-vessel wall interaction in isolated human arteries suspended in organ chambers for isometric tension recording. Methods and Results: In arteries with endothelium, thrombin (0.01 to 1 U/mL) induced endothelium-dependent relaxations, which were reduced by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 10-4 mol/L) and/or indomethacin (10-5 mol/L). Human platelets (75 000/μL) evoked only marginal contractions in arteries with endothelium (3±3% of the contraction to KCl 100 mmol/L; NS), which were markedly enhanced by endothelial removal (22±4%; P