Studies on thrombin-induced endothelium-dependent vascular effects.

The clotting enzyme thrombin induces not only blood coagulation but it also receptor-mediated cellular events. In our studies, thrombin at nanomolar concentrations caused irreversible aggregation of washed human platelets which was inhibited by the naturally occurring tight-binding inhibitor hirudin. Thrombin within the same concentration range caused concentration-dependent transient relaxation of PGF2 alpha-precontracted pig coronary artery ring segments with intact endothelium. The relaxant response was neither affected by indomethacin nor by verapamil and was only slightly inhibited by exposure to calcium-free medium. Methylene blue enhanced the PGF2 alpha-induced contraction and diminished the thrombin-induced relaxation. Hirudin inhibited the relaxant effect of thrombin in a concentration-dependent manner. After removal of the endothelium by mechanical rubbing the thrombin-induced relaxation was absent. The present studies suggest that thrombin generated during coagulation is able to modify the vascular smooth muscle tone.