Potassium Channel Openers Relax A23187-Induced Nifedipine-Resistant Contraction of Rat Aorta

We investigated the vasorelaxant mechanisms of three potassium channel openers (PCOs: NIP-121, cromakalim, and nicorandil) using rat aortic strips precontracted with calcium ionophore A23187. A23187 (10(-6) M)-induced contraction was fully relaxed by NIP-121, cromakalim, and nicorandil, but not by the calcium channel blocker nifedipine. The effective concentration range and potency of these relaxant effects were the same as those previously reported for relaxation caused by potassium channel opening in the presence of 30 mM K+ or for relaxation of agonist-induced contraction. Relaxation induced by NIP-121 or cromakalim was competitively antagonized by glibenclamide, with apparent pA2 values for NIP-121 and cromakalim of 7.28 and 7.47, respectively. However, these PCOs did not relax A23187-induced contraction in the presence of 50 mM K+ and 10(-6) M nifedipine. These PCOs but not nifedipine significantly inhibited calcium-induced contraction in the presence of A23187 (10(-6)M). NIP-121, cromakalim, and nicorandil induced full relaxation of A23187-precontracted arteries, which might be attributable (partially for nicorandil) to their potassium channel opening activity. This relaxant effect might be related to inhibition of A23187-induced calcium influx resulting from opening of glibenclamide-sensitive potassium channels.