Vasorelaxant action of Ki1769, a new pyridinecarboximidamide, in isolated porcine coronary artery

The characteristics of KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethansulfonate) and its phenethyl and 2-hydroxyethyl derivatives (Ki1769 and Ki3315) were studied in isolated porcine coronary arteries. KRN2391, Ki1769 and Ki3315 produced concentration-dependent relaxation of coronary arteries contracted by 25 mM KCl and the order of relaxant potency was KRN2391 > Ki1769 > Ki3315. At the maximum effect, KRN2391 produced nearly complete relaxation but Ki1769 produced about 66% relaxation. The maximum effect of Ki3315 could not be obtained because of its solubility. The relaxation induced by KRN2391 was antagonized by glibenclamide and methylene blue but relaxations caused by Ki1769 and Ki3315 were antagonized by glibenclamide alone. The antagonistic effect of glibenclamide on Ki1769- and Ki3315-induced relaxations was more potent than that on KRN2391-induced relaxation. KRN2391 induced relaxation of coronary arteries contracted by 40 mM KCl in a concentration-dependent manner but the effect of KRN2391 was smaller against 40 mM KCl-induced contractions than against 25 mM KCl-induced contractions. Ki1769 had almost no effect on coronary arteries contracted by 40 mM KCl. These results suggest that pyridinecarboximidamide derivatives which do not possess a nitroxyl group have vasodilating ability based on a K+ channel opening action.