Endothelium-dependent relaxant effect of thrombin on isolated pig coronary arteries

In pig coronary arteries with intact endothelium the clotting enzyme thrombin at physiologically relevant concentrations caused a reversible transient and concentration-dependent relaxation of PGF2 alpha-precontracted vessels which was absent in case of mechanically removed endothelium. The thrombin-induced relaxation was not affected by indomethacin. Exposure of the coronary arteries to a calcium-free medium or preincubation with verapamil led to the reduction of the PGF2 alpha-induced contraction while the relaxant effect of thrombin was only slightly inhibited. However, the guanylate cyclase inhibitor methylene blue diminished the relaxant response to thrombin. The specific tight-binding thrombin inhibitor hirudin prevented the relaxant effect of thrombin in a concentration-dependent manner.