Inoue T, Ito Y, Takeda K
Br J Pharmacol. 1983 Nov;80(3):459-70. doi: 10.1111/j.1476-5381.1983.tb10716.x.
The effects of 2-nicotinamidoethyl nitrate (nicorandil; 2-NN), a synthesized coronary vasodilator, on smooth muscle cells of dog mesenteric artery or trachea were investigated using microelectrode, double sucrose gap and isometric tension recording methods. Nicorandil hyperpolarized the smooth muscle membrane of the mesenteric artery (5 X 10(-6)M) and the trachea (5 X 10(-5)M). In both these smooth muscle cells, the nicorandil-induced hyperpolarization remained constant in various concentrations of [Cl-]o, but changed with various concentrations of [K+]o. This hyperpolarization was partly inhibited following pretreatment with tetraethylammonium (TEA greater than 1 mM) and was completely inhibited following pretreatment with procaine (1 mM or 5 mM), indicating that the nicorandyl-induced hyperpolarization is due to increase in the K-conductance, in both these membranes. Following pretreatment with TEA (5 mM), outward current pulses evoked an action potential in tracheal smooth muscle cells. Nicorandil inhibited the generation of action potential due to the hyperpolarization of the membrane but not due to inhibition of the spike generating mechanism. Nicorandil (10(-6)M) inhibited the contracture evoked by excess [K]o, in both tissues. The contracture evoked by noradrenaline or repetitive field stimulation with short duration (50 microseconds) pulses was also inhibited in the mesenteric artery, while a higher dose of nicorandil (10(-5)M) was required to inhibit the contracture evoked by acetylcholine or repetitive field stimulation in the trachea. Excitatory junction potentials (e.j.ps) evoked by field stimulation in the mesenteric artery due to the release of noradrenaline, or in the trachea due to release of acetylcholine, were suppressed by 10(-5)M or 5 X 10(-5)M nicorandil, respectively. The reduction in the amplitude of e.j.p. was mainly due to the hyperpolarization of the membrane with increase in the membrane conductance. In the mesenteric artery, following pretreatment with TEA (1 mM) an action potential was generated on the e.j.p.. Nicorandil suppressed the generation of the action potential by reduction in the amplitude of the e.j.p., below the threshold required for generation of the action potential. These results indicate that nicorandil hyperpolarizes the membrane by increasing K-conductance and inhibits the generation of contraction, in both tissues. Higher concentrations of nicorandil are required to suppress the mechanical response in the trachea than in the mesenteric artery. Depression of the mechanical responses in both tissues is partly due to suppression of Ca-mobilization inside the muscle cells and partly to hyperpolarization of the membrane.
使用微电极、双蔗糖间隙和等长张力记录方法，研究了合成的冠状血管扩张剂2-烟酰胺基乙基硝酸盐（尼可地尔；2-NN）对犬肠系膜动脉或气管平滑肌细胞的影响。尼可地尔使肠系膜动脉（5×10⁻⁶M）和气管（5×10⁻⁵M）的平滑肌膜超极化。在这两种平滑肌细胞中，尼可地尔诱导的超极化在不同浓度的[Cl⁻]ₒ中保持恒定，但随不同浓度的[K⁺]ₒ而变化。用四乙铵（TEA大于1 mM）预处理后，这种超极化部分受到抑制，用普鲁卡因（1 mM或5 mM）预处理后则完全受到抑制，这表明在这两种膜中，尼可地尔诱导的超极化是由于K⁺电导增加所致。用TEA（5 mM）预处理后，外向电流脉冲在气管平滑肌细胞中诱发动作电位。尼可地尔抑制动作电位的产生是由于膜的超极化，而不是由于抑制了锋电位产生机制。尼可地尔（10⁻⁶M）在两种组织中均抑制了由过量[K]ₒ诱发的挛缩。去甲肾上腺素或短持续时间（50微秒）脉冲的重复场刺激诱发的挛缩在肠系膜动脉中也受到抑制，而在气管中则需要更高剂量的尼可地尔（10⁻⁵M）来抑制乙酰胆碱或重复场刺激诱发的挛缩。由场刺激在肠系膜动脉中由于去甲肾上腺素释放而诱发的兴奋性接头电位（e.j.ps），或在气管中由于乙酰胆碱释放而诱发的兴奋性接头电位，分别被10⁻⁵M或5×10⁻⁵M尼可地尔抑制。e.j.p.幅度的降低主要是由于膜的超极化以及膜电导的增加。在肠系膜动脉中，用TEA（1 mM）预处理后，在e.j.p.上产生动作电位。尼可地尔通过降低e.j.p.的幅度，使其低于产生动作电位所需的阈值，从而抑制动作电位的产生。这些结果表明，尼可地尔通过增加K⁺电导使膜超极化，并在两种组织中抑制收缩的产生。与肠系膜动脉相比，在气管中需要更高浓度的尼可地尔来抑制机械反应。两种组织中机械反应的抑制部分是由于抑制了肌肉细胞内的Ca²⁺动员，部分是由于膜的超极化。
