Potassium channel opening properties of a novel compound, NIP-121, cromakalim and nicorandil in rat aorta and portal vein.

A novel compound, NIP-121, cromakalim and nicorandil caused concentration-dependent relaxation of rat aortas precontracted with 30 mM KCl, with pEC50 (M) values of 8.2, 7.1 and 5.5, respectively. At 60 mM KCl, the vasorelaxation induced by NIP-121 or cromakalim was almost abolished whereas that induced by nicorandil remained. In preparations precontracted with prostaglandin F2 alpha(PGF2 alpha) (10(-5) M), glibenclamide (10(-7) M) and phentolamine (3 x 10(-6), 3 x 10(-5) M) antagonized the relaxation induced by NIP-121 and cromakalim but not that induced by nicorandil. Methylene blue (10(-5) M) showed antagonistic effects against the vasorelaxation induced by nicorandil but not that induced by NIP-121. NIP-121 (10(-7), 10(-6) M) and cromakalim (10(-6), 10(-5) M) significantly increased the 86Rb+ efflux rate in rat aorta. The three compounds inhibited the frequency of spontaneous contractions of the rat portal vein (pIC30; NIP-121 = 8.0, cromakalim = 7.1 and nicorandil = 4.9); glibenclamide and phentolamine antagonized the effects of these compounds. In conclusion, NIP-121 is a more potent K+ channel opener than cromakalim in these tissues. Nicorandil apparently behaves as a K+ channel opener in the rat portal vein, but the vasorelaxation may involve some other mechanisms, such as generation of cyclic GMP.