COMPARISON OF THE ANTI-VASOCONSTRICTOR EFFECTS OF A NOVEL VASODILATORKRN2391, NICORANDIL AND NIFEDIPINE ON ISOLATED PORCINE LARGE CORONARY-ARTERY

The anti-vasoconstrictor profile of KRN2391, a novel vasodilator, was compared with that of nicorandil and nifedipine in isolated porcine la rge coronary arteries contracted by KCl, noradrenaline, serotonin, ace tylcholine, endothelin-1 and U46619, a thromboxane A2 analogue. KRN239 1 (10(-8) - 3 x 10(-5) M), nicorandil (10(-7) - 3 x 10(-4) M) and nife dipine (10(-10) - 10(-5) M) inhibited these contractile responses in a concentration-dependent manner. KRN2391 and nicorandil completely abo lished these contractile responses at their maximum effects. However, nifedipine caused less inhibition than KRN2391 and nicorandil and did not completely abolish the contractile responses. The relaxant activit y of KRN2391 was more potent than that of nicorandil. This study shows that the anti-vasoconstrictor profiles of KRN2391, nicorandil and nif edipine involve different relaxant mechanisms.