VASORELAXANT MECHANISM OF KRN2391 AND NICORANDIL IN PORCINE CORONARY-ARTERIES OF DIFFERENT SIZES

1 The relaxant mechanisms of action of KRN2391, a novel vasodilator, a nd nicorandil on epimyocardial coronary artery (2.5-3.0 mm outer diame ter) and mid-myocardial coronary artery (0.8-1.0 mm outer diameter) we re investigated in porcine isolated coronary arteries. In addition, th e vasorelaxant responses of KRN2391 and nicorandil were compared with those of nitroglycerin and cromakalim, a K+ channel opener, in epi- an d mid-myocardial coronary arteries. 2 Nitroglycerin showed a more pote nt relaxant effect on epi-myocardial coronary arteries than on mid-myo cardial coronary arteries, whereas cromakalim produced greater relaxat ion responses in mid-myocardial coronary arteries. There was no differ ence between epi- and mid-myocardial coronary arteries in terms of the relaxant effect of KRN2391 and nicorandil. 3 Relaxation induced by KR N2391 in epi- and mid-myocardial coronary arteries was inhibited by ox yhaemoglobin, a pharmacological antagonist of nitrovasodilators, and g libenclamide, a pharmacological antagonist of K+ channel opening drugs . However, the inhibitory effect of glibenclamide on KRN2391-induced r elaxation was greater in mid-myocardial coronary artery than in epi-my ocardial coronary artery. 4 Relaxation induced by nicorandil was inhib ited by oxyhaemoglobin alone in epi-myocardial coronary arteries and b y both oxyhaemoglobin and glibenclamide in mid-myocardial coronary art eries. 5 In epi- and mid-myocardial coronary arteries, relaxation indu ced by cromakalim was inhibited by glibenclamide but not by oxyhaemogl obin, whereas relaxation induced by nitroglycerin was inhibited by oxy haemoglobin but not by glibenclamide. 6 These results suggest that KRN 2391 and nicorandil exhibit a dual mechanism of action acting partly a s a nitrate and partly as a K+ channel opener. The mechanism of action of these drugs depend on the segment of coronary artery studied. Furt hermore, the dual mechanism of action of KRN2391 and nicorandil seems to contribute to the equipotent relaxant effect between epi- and mid-m yocardial coronary arteries.