Effect of KRN2391, a novel vasodilator, on endothelin-1-induced contraction of porcine coronary artery: comparison with cromakalim, nitroglycerin and nifedipine.

The relaxant effects of KRN2391 (K channel opener and nitrate-like), cromakalim (K channel opener), nitroglycerin (nitrate-like) and nifedipine (Ca channel blocker) were investigated in porcine isolated coronary arteries contracted by endothelin-1 and KCl. KRN2391, nitroglycerin and cromakalim concentration-dependently inhibited the 10(-8) M endothelin-1-induced contraction, but less potently inhibited the 40 mM KCl-induced contraction. Nifedipine concentration-dependently inhibited the 40 mM KCl-induced contraction more strongly than the 10(-8) M endothelin-1-induced contraction. KRN2391 and nitroglycerin produced a complete relaxation of arteries contracted by endothelin-1 at its maximum effect. Cromakalim and nifedipine, both at 3 x 10(-5) M, produced 83.9% and 73.3% of the complete relaxation of the endothelin-1-induced contraction, respectively. In the 40 mM KCl-induced contraction, nifedipine produced a complete relaxation, but KRN2391, cromakalim and nitroglycerin, all at 3 x 10(-5) M, produced a relaxation of 62.7%, 27.1% and 79.4%, respectively. The combination of cromakalim and nitroglycerin relaxed the 10(-8) M endothelin-1- and 40 mM KCl-induced contractions in a concentration-dependent manner. The relaxant effect of this combination was greater against the endothelin-1-induced contraction than against the 40 mM KCl-induced contraction. The maximum relaxation of the combination of cromakalim (3 x 10(-5) M) and nitroglycerin (3 x 10(-6) M) was complete for the endothelin-1-induced contraction but a relaxation of 77.8% was obtained for the 40 mM KCl-induced contraction, i.e. the relaxant effects using this combination were greater than those by cromakalim (3 x 10(-5) M) alone.(ABSTRACT TRUNCATED AT 250 WORDS)