Yamashita T, Masuda Y, Tanaka S
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Saitama, Japan.
J Cardiovasc Pharmacol. 1994 Dec;24(6):914-20. doi: 10.1097/00005344-199424060-00008.
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.
我们使用钙离子载体A23187预收缩的大鼠主动脉条，研究了三种钾通道开放剂（PCOs：NIP - 121、克罗卡林和尼可地尔）的血管舒张机制。NIP - 121、克罗卡林和尼可地尔可完全舒张A23187（10⁻⁶ M）诱导的收缩，但钙通道阻滞剂硝苯地平则不能。这些舒张作用的有效浓度范围和效能与先前报道的在30 mM K⁺存在时钾通道开放引起的舒张或激动剂诱导收缩的舒张情况相同。NIP - 121或克罗卡林诱导的舒张被格列本脲竞争性拮抗，NIP - 121和克罗卡林的表观pA2值分别为7.28和7.47。然而，在50 mM K⁺和10⁻⁶ M硝苯地平存在时，这些PCOs并不能舒张A23187诱导的收缩。在A23187（10⁻⁶ M）存在时，这些PCOs而非硝苯地平可显著抑制钙诱导的收缩。NIP - 121、克罗卡林和尼可地尔可使A23187预收缩的动脉完全舒张，这可能（尼可地尔部分如此）归因于它们的钾通道开放活性。这种舒张作用可能与抑制由格列本脲敏感钾通道开放引起的A23187诱导的钙内流有关。
