PLASMIN-INDUCED ENDOTHELIUM-DEPENDENT VASODILATATION VERSUS FIBRINOLYSIS - 2 PATHWAYS OF BLOOD-FLOW RESTORATION IN THE THROMBOTICALLY OCCLUDED VESSELS

Human plasmin at pharmacologically relevant concentrations caused a ra pid relaxation of the perfused rat tail artery preconstricted by norad renaline. Plasmin-induced relaxation was dependent upon the presence o f vascular endothelium. This endothelial effect was inhibited by the n itric oxide blocker N-G-Nitro-L-Arginine. Antibodies to pre-/kallikrei n and to low molecular weight/high molecular weight kininogen did not suppress the Pm-induced vasodilatation, while epsilon-aminocaproic aci d and aprotinin did. The vasorelaxant effect of plasmin was dependent on the enzyme active site. Activation of the endothelium-hound plasmin ogen by urokinase or tissue-type plasminogen activator, as well as a p erfusion of the isolated artery by streptokinase-activated plasma indu ced a vessel relaxation. Our data suggest that plasmin formed in the b lood stream or on the surface of vascular endothelium produces the end othelium-dependent nitric oxide-mediated vasodilatation.