VASORELAXANT ACTION OF KI1769, A NEW PYRIDINECARBOXIMIDAMIDE, IN ISOLATED PORCINE CORONARY-ARTERY

The characteristics of KRN2391 yano-N'-(2-nitroxyethyl)-3-pyridinecarb oximidamide monomethansulfonate) and its phenethyl and 2-hydroxyethyl derivatives (Ki1769 and Ki3315) were studied in isolated porcine coron ary arteries. KRN2391, Ki1769 and Yi3315 produced concentration-depend ent relaxation of coronary arteries contracted by 25 mM KCl and the or der of relaxant potency was KRN2391 > Yi1769 > Ki3315. At the maximum effect, KRN2391 produced nearly complete relaxation but Ki1769 produce d about 66% relaxation. The maximum effect of Ki3315 could not be obta ined 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 ant agonistic effect of glibenclamide on Ki1769- and Ki3315-induced relaxa tions 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 a gainst 40 mM KCl-induced contractions than against 25 mM KCl-induced c ontractions. Ki1769 had almost no effect on coronary arteries contract ed by 40 mM KCl. These results suggest that pyridinecarboximidamide de rivatives which do not possess a nitroxyl group have vasodilating abil ity based on a K+ channel opening action.