Kamigaki M, Ichihara K, Kohgo Y, Abiko Y
Third Department of Internal Medicine, Asahikawa Medical College, 4-5 Nishikagura, Asahikawa 078, Japan.
Eur J Pharmacol. 1995 Dec 12;287(2):121-6. doi: 10.1016/0014-2999(95)00480-7.
Glibenclamide, an ATP-sensitive K (K ATP) channel blocker, worsens the ischemia-induced metabolic derangement in the heart through inhibition of K ATP channels. We examined whether the hypoglycemic effect of glibenclamide was involved in the worsening of myocardial energy metabolism during ischemia. Pentobarbital-anesthetized dogs were subjected to 15-min ligation of the left anterior descending coronary artery. Either vehicle (dimethyl sulfoxide, DMSO) or glibenclamide (1 mg/kg) was injected i.v. 10 min before the ligation. In half of the animals given glibenclamide, glucose was continuously infused at 3 mg/kg per min immediately after glibenclamide injection. Glibenclamide increased the serum insulin level and decreased the blood glucose level. Glucose infusion completely abolished the hypoglycemia due to glibenclamide. Glibenclamide enhanced the decrease in ATP and total adenine nucleotides and increase in tissue lactate caused by ischemia. Glucose infusion did not cancel the augmentation of ischemia-induced alterations of myocardial energy metabolism caused by glibenclamide. These results suggest that K ATP channels directly play an important role in endogenous mechanisms of myocardial protection against ischemic damage.
格列本脲是一种ATP敏感性钾（KATP）通道阻滞剂，它通过抑制KATP通道，使心脏缺血诱导的代谢紊乱恶化。我们研究了格列本脲的降糖作用是否参与了缺血期间心肌能量代谢的恶化。用戊巴比妥麻醉的犬，结扎左冠状动脉前降支15分钟。在结扎前10分钟静脉注射溶剂（二甲基亚砜，DMSO）或格列本脲（1mg/kg）。在给予格列本脲的动物中，一半在注射格列本脲后立即以3mg/kg每分钟的速度持续输注葡萄糖。格列本脲提高了血清胰岛素水平并降低了血糖水平。葡萄糖输注完全消除了由格列本脲引起的低血糖。格列本脲增强了缺血导致的ATP和总腺嘌呤核苷酸的降低以及组织乳酸的增加。葡萄糖输注并未消除格列本脲引起的缺血诱导的心肌能量代谢改变的增强。这些结果表明，KATP通道在心肌保护免受缺血损伤的内源性机制中直接发挥重要作用。
