FIBRINOGEN MEDIATES VASOACTIVE EFFECTS IN SAPHENOUS-VEIN BY AN ICBM-1DEPENDENT PATHWAY

Objective: To investigate whether fibrinogen or its products had direc t vasoactive effects on saphenous vein rings. Subjects and Methods: Th e vasomotor tone of saphenous vein rings, harvested from patients unde rgoing bypass surgery (n = 24) or high ligation for correction of vari cose veins (n = 32) in a Regional Vascular Unit, was investigated unde r conditions of isometric tension. Main outcome measures: Endothelium- dependent and endothelium-independent changes in vasomotor tone in res ponse to fibrinogen and its products. Results: Saphenous vein rings ex hibited endothelium-dependent relaxation in response to fibrinogen, ma ximum relaxation 63 +/- 5% at 1.8 mu M fibrinogen. Fibrinopeptides, fr agment D, and the fragment D.fragment E complex (fgD.fgE) had no vasoa ctive effects. Preincubation of vein rings with fgD.fgE abolished the fibrinogen-mediated relaxation: fragment D had no effect. Preincubatio n of vein rings with antibodies to ICAM-1 effected a dose-dependent in hibition of fibrinogen-mediated relaxation. Conclusion: Fibrinogen bin ding to endothelial receptors (ICAM-1) causes the release of vasoactiv e mediators.