Sumimoto K, Domae M, Yamanaka K, Nakao K, Hashimoto T, Kitamura K, Kuriyama H
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Cardiovasc Pharmacol. 1987;10 Suppl 8:S66-75.
The action of nicorandil on vascular smooth muscles has been studied in vitro using the microelectrode, Ca-transient, isometric tension recording methods, and the bioassay methods of cyclic nucleotides and inositol phospholipids. Nicorandil increased Ca-insensitive K conductance and hyperpolarized the membrane and thus prevented the activation of the voltage-dependent Ca channel. The hyperpolarization occurred to a greater extent in venous tissue than in arterial tissue. Nicorandil stimulated the synthesis of cyclic guanosine monophosphate (cGMP) in the polarized and depolarized muscle tissues, as did nitroglycerin. Consequently, nicorandil reduces the concentrations of free Ca in the myoplasm, due to acceleration of the Ca pump at the sarcolemma, and may prevent the phosphorylation of myosin through phosphorylation of myosin light chain kinase. These actions of nicorandil may not contribute to the synthesis of inositol-1,4,5-trisphosphate hydrolyzed from phosphatidylinositol-4,5-bisphosphate. The above actions of nicorandil--hyperpolarization and increase in the cyclic GMP--may cause relaxation of the tissues precontracted by various stimulants.
已采用微电极、钙瞬变、等长张力记录方法以及环核苷酸和肌醇磷脂生物测定方法，在体外研究了尼可地尔对血管平滑肌的作用。尼可地尔增加了对钙不敏感的钾电导并使膜超极化，从而阻止了电压依赖性钙通道的激活。超极化在静脉组织中比在动脉组织中更为明显。尼可地尔与硝酸甘油一样，刺激了极化和去极化肌肉组织中环磷酸鸟苷（cGMP）的合成。因此，尼可地尔由于加速了肌膜上的钙泵，降低了肌浆中游离钙的浓度，并可能通过肌球蛋白轻链激酶的磷酸化来阻止肌球蛋白的磷酸化。尼可地尔的这些作用可能与从磷脂酰肌醇 - 4,5 - 二磷酸水解而来的肌醇 - 1,4,5 - 三磷酸的合成无关。尼可地尔的上述作用——超极化和cGMP增加——可能导致被各种刺激物预收缩的组织松弛。
