Effects of 2-nicotinamidoethyl nitrate (SG-75, nicorandil) on indomethacin-induced contractions of isolated dog coronary arteries.

Effects of 2-nicotinamidoethyl nitrate (SG-75) on contractile responses of dog coronary arteries to indomethacin were investigated in vitro. Indomethacin (3 X 10(-8) and 3 X 10(-7) Gm/ml) produced contractions of isolated coronary arterial strips, which were reproduced by successive administration of the drug. SG-75 (10(-5) Gm/ml) administered 5 min prior to indomethacin, significantly depressed indomethacin-induced contractions of the strips. In coronary arterial strips under potassium-contracture, SG-75 10(-8)-10(-4) Gm/ml) produced concentration-dependent relaxations, which were not affected by prior administration of indomethacin (3 X 10(-6) Gm/ml). Tranylcypromine (10(-4) Gm/ml) did not influence the relaxant responses of the strips to SG-75 (10(-8)-10(-5) Gm/ml) but significantly depressed them to SG-75 (10(-4) Gm/ml). Results indicate that large doses of SG-75 will induce a relaxant effect on isolated dog coronary arteries through activation of intravascular biosynthesis or release of prostacyclin from vascular tissues.