title: Studies on thrombin-induced endothelium-dependent vascular effects.
abstract: 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.
authors.affiliation: Institute of Pharmacology and Toxicology, Medical Academy Erfurt, GDR.
authors.forename: E
authors.initials: E
authors.lastname: Glusa
authors.forename: F
authors.initials: F
authors.lastname: Markwardt
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010974:Platelet Aggregation; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D006629:Hirudins; D015237:Dinoprost; D014700:Verapamil; D013917:Thrombin; D001920:Bradykinin; D007213:Indomethacin