[The endothelium and antithrombotic substances]

Thrombin is a component of the coagulation cascade which leads to the formation of fibrin. In platelets, thrombin promotes aggregation. Thrombin not only interfers with hemostasis, but also exerts profound vascular effects. In canine coronary arteries, thrombin leads to endothelium-dependent relaxations via the production of endothelium derived relaxing factor. Higher concentrations, however, lead to contractions. Without endothelium the relaxations are abolished whereas the contractions may be augmented. In ischemic coronary arteries same reactions could be observed. Antithrombotic substances like heparin or hirudin inhibit the vascular effects of thrombin. Heparin binds in the proximity of the catalytic sites, whereas the bindings sites for hirudin can be found in the anionic group of the enzyme. Furthermore, heparin interacts with platelets and fibrinolytic substances and may be inactivated. Recombinant hirudin, however, is a selective thrombin antagonist, does not influence vascular smooth muscle tonus and does not lead to bleeding. Thus, hirudin may be an ideal substance for treating thrombin-induced vasospasm in coronary heart disease.