Plasmin-induced endothelium-dependent vasodilatation versus fibrinolysis — Two pathways of blood flow restoration in the thrombotically occluded vessels?

Abstract

Human plasmin at pharmacologically relevant concentrations caused a rapid relaxation of the perfused rat tail artery preconstricted by noradrenaline. Plasmin-induced relaxation was dependent upon the presence of vascular endothelium. This endothelial effect was inhibited by the nitric oxide blocker N G-Nitro-L-Arginine. Antibodies to pre-/kallikrein and to low molecular weight/high molecular weight kininogen did not suppress the Pin-induced vasodilatation, while e-aminocaproic acid and aprotinin did. The vasorelaxant effect of plasmin was dependent on the enzyme active site. Activation of the endothelium-bound plasminogen by urokinase or tissue-type plasminogen activator, as well as a perfusion of the isolated artery by streptokinase-activated plasma induced a vessel relaxation. Our data suggest that plasmin formed in the blood stream or on the surface of vascular endothelium produces the endothelium-dependent nitric oxide-mediated vasodilatation.