Endothelium-dependent relaxant effect of thrombocytin, a serine proteinase from Bothrops atrox snake venom, on isolated pig coronary arteries.

Since thrombin causes an endothelium-dependent relaxation of precontracted pig coronary arteries, the ability of thrombocytin, a serine proteinase from the venom of the common lancehead, Bothrops atrox, to induce endothelium-dependent changes in the vascular tone was investigated. Relaxation of pig coronary rings did not appear in vessels denuded of the endothelium. Thrombocytin (0.1-2.0 micrograms/ml) caused an endothelium-dependent, reversible, transient relaxation of PGF2 alpha-precontracted arteries which could be blocked by heparin and relatively high concentrations of alpha-NAPAP, a synthetic competitive thrombin inhibitor. Indomethacin and hirudin did not influence the relaxant effect. Both the thrombocytin- and bradykinin-induced relaxation were diminished by the guanylate cyclase inhibitor methylene blue and by NG-monomethyl-L-arginine. The thrombocytin-induced relaxation was absent in de-endothelialized vessels. Thrombocytin was able to induce aggregation of human blood platelets in Tyrode's solution at the same concentration range as used for the relaxation. Batroxobin neither relaxed precontracted arteries nor aggregated human blood platelets in vitro. The present studies show that the serine proteinase thrombocytin is not only able to aggregate platelets but may also release endothelium-derived relaxing factor from the vascular endothelium.