CHARACTERISTICS OF KI1769, A NOVEL VASODILATOR, IN ISOLATED RAT AORTA

The vasorelaxant mechanism of a newly synthesized vasodilator, Ki1769 cyano-N'-(2-phenethyl)-3-pyridinecarboximidamide], was studied in isol ated rat aorta in comparison with cromakalim. Ki1769 (10(-8)-10(-5) M) and cromakalim (10(-8)-10(-5) M) produced a concentration-dependent r elaxation and the EC50 values for Ki1769 and cromakalim were (8.60 +/- 1.90) x 10(-7) M and (1.36 +/- 0.18) x 10(-7) M, respectively. Ki1769 - and cromakalim-induced relaxations were competitively antagonized by glibenclamide with pA2 values of 6.83 and 6.93, respectively. Charybd otoxin, apamine, atropine, propranolol and indomethacin did not affect the Ki1769-induced relaxation. An increase in Rb-86 efflux was induce d by Ki1769. Glibenclamide attenuated the increase in Rb-86 efflux pro duced by Ki1769. These results suggest that the vasorelaxant effect of Ki1769 is based on the glibenclamide-sensitive K channel-opening acti on.