权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

THE ROLE OF ATP-SENSITIVE POTASSIUM CHANNELS IN THE MECHANISMS OF METABOLIC CORONARY VASODILATION

ATP 敏感钾通道在代谢性冠状血管舒张机制中的作用

基本信息

批准号：
06670725
负责人：
EGASHIRA Kensuke
金额：
$ 1.54万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670725/
关键词：
ATP-sensitive potassium channels coronary circulation metabolic coronary vasodilation glibenclamide dogs

项目摘要

1) Effects of glibenclamide (an inhibitor of ATP-sensitive potassium channels) on metabolic coronary vasodilationExperiments were performed in anesthetized and conscious dogs. Increasing heart rate from 100 to 160 bpm increased coronary blood flow without altering other hemodynamic parameters. Glibenclamide (1.5 and 5.0 mug/kg・min) significantly inhibited coronary vasodilation induced by pacing tachycardia, while it did not affect coronary vasodilation induced by acetylcholine and nitroglycerin. Glibenclamide completely abolished coronary vasodilation induced by pinacidil. These results suggest that metabolic coronary vasodilation is mediated at least in part by ATP-sensitive potassium channels.2) Effects of Pinacidil (ATP-sensitive potassium channel opener) on metabolic coronary vasodilationExperiments were performed in anesthetized dogs. Intracoronary infusion of denopamine (a selective beta1-adrenoceptor agonist) increased coronary blood flow associated with an increase in myocardial inotropic state. Pinacidil 1 mug/min, that had no effects on basal hemodynamic parameters but modestly increased coronary blood flow by 10% or less, augmented coronary vasodilation induced by denopamine, while denopamine-induced changes in myocardial inotropic state and myocardial oxygen consumption were comparable before and after pinacidil.Pinacidil did not affect coronary vasodilation induced by acetylcholine, nitroglycerin, and beta2-adrenoceptor stimulation. Denopamine-induced coronary vasodilation was completely inhibited by a selective beta1 adrenoceptor antagonist bisoprolol. These results suggest that ATP-sensitive potassium channel opener pinacidil augments metabolic coronary vasodilation induced by beta1-adrenoceptor stimulation.

1）格列本脲（ATP敏感钾通道抑制剂）对代谢性冠状动脉舒张的影响实验在麻醉和清醒的狗中进行。将心率从 100 bpm 增加至 160 bpm 可增加冠状动脉血流量，而不会改变其他血流动力学参数。格列本脲（1.5和5.0μg/kg·min）显着抑制起搏心动过速引起的冠状血管舒张，但不影响乙酰胆碱和硝酸甘油引起的冠状血管舒张。格列本脲完全消除了吡那地尔引起的冠状动脉舒张作用。这些结果表明，代谢性冠状动脉血管舒张至少部分是由ATP敏感性钾通道介导的。2)吡那地尔(ATP敏感性钾通道开放剂)对代谢性冠状动脉血管舒张的影响实验在麻醉犬中进行。冠状动脉内输注地诺巴明（一种选择性β1-肾上腺素受体激动剂）可增加冠状动脉血流量，并增强心肌正性肌力状态。吡那地尔1杯/分钟，对基础血流动力学参数没有影响，但适度增加冠脉血流量10%或更少，增强地诺巴明诱导的冠状血管舒张，而地诺巴明引起的心肌正性肌力状态和心肌耗氧量的变化在吡那地尔前后相当。吡那地尔不影响地诺巴明诱导的冠状血管舒张。通过乙酰胆碱、硝酸甘油和β2-肾上腺素受体刺激。地诺帕明诱导的冠状动脉舒张可被选择性 β1 肾上腺素受体拮抗剂比索洛尔完全抑制。这些结果表明，ATP 敏感的钾通道开放剂吡那地尔可增强由 β1 肾上腺素受体刺激引起的代谢性冠状动脉舒张。