Contribution of mitochondrial K_<ATP> channel to cardioprotection against hypoxia or ischemia in rat cultured myocytes and isolated blood-perfused hearts

1. 本研究旨在研究血管紧张素转换酶抑制剂替莫普利是否通过肌层K_<ATP>通道和/或线粒体K_<ATP>通道直接保护心肌细胞免受缺氧/再氧化损伤。原代培养的新生大鼠心肌细胞缺氧5小时，随后再充氧2小时。通过乳酸脱氢酶（LD）的释放来评估肌细胞损伤。替莫普利以剂量依赖性的方式显著抑制缺氧/再氧合后的LD释放。Pinacidil和diazoxide能略微降低LD的释放。格列本脲和5-羟基癸酸并没有减弱替莫april对培养心肌细胞释放LD的心脏保护作用。我们的研究结果表明，血管紧张素转换酶抑制剂不靶向K_<ATP>通道对缺氧/再氧损伤的龋保护机制。2. 本研究旨在探讨左室舒张末压（LVEDP）升高引起的心肌舒张、舒张末压（LVEDP）升高激活K_<ATP>是否为缺血后心肌形成的先决条件。血液灌注的心脏局部无血流缺血20分钟，再灌注30分钟。对照组LVEDP设为10 mmHg。拉伸组LVEDP升高至30或60 mmHg，缺血前5min。经缓冲灌注的心脏局部缺血30分钟，再灌注30分钟。拉伸组LVEDP在缺血前5 min或15 min分别升高至30或60 mmHg。30mmhg -牵张组和60mmhg -牵张组血液灌注心脏30min血流动力学参数均有改善，缓冲灌注心脏30mmhg -牵张组血流动力学参数呈牵张时间依赖性。增加LVEDP通过不涉及心肌缺血的机制对血灌注和缓冲灌注大鼠心脏进行预调节，诱导心肌拉伸。少

1. The present study was designed to examine whether an angiotensin-converting enzyme inhibitor, temocapril, directly protects cardiac myocytes against hypoxia/reoxygenation injury via sarcolemmal K_<ATP> channel and/or mitochondrial K_<ATP> channel. Neonatal rat cardiac myocytes in primary culture were exposed to hypoxia for 5 hours and subsequently reoxygenated for 2 hours. Myocytes injury was estimated by the release of lactate dehydrogenase (LD). Temocapril significantly inhibited LD release after hypoxia/re-oxygenation in a dose-dependent manner. Pinacidil and diazoxide decreased LD release slightly. Glibenclamide, and 5-hydroxy-decanoic acid did not attenuate a cardioprotective effect of temocapril on LD release from cultured myocytes. Our results demonstrate that an angiotensin-converting enzyme inhibitor does not target K_<ATP> channel on the mechanism of carioprotection against hypoxia/reoxygenation injury. 2. The aim of the study was to determine whether myocardial stretch, w … More hich was proposed to activate K_<ATP>, caused by an increase in left ventricular end-diastolic pressure (LVEDP) could precondition post-ischemic myocardium. The blood-perfused hearts were subjected to 20 min of global no-flow ischemia followed by 30 min of reperfusion. In control group, LVEDP was set at 10 mmHg. In stretch group, LVEDP was increased to 30 or 60 mmHg for 5 min before global ischemia. The buffer-perfused hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. In stretch group, LVEDP was increased to 30 or 60 mmHg for 5 min or 15 min before global ischemia. Hemodynamic parameters at 30 min of reperfusion improved in both 30 mmHg- and 60 mmHg-stretch groups of blood-perfused hearts, and in 30 mmHg-stretch group of buffer-perfused hearts in stretch-duration time dependent way. Myocardial stretch induced by increasing LVEDP preconditioned both blood-perfused and buffer-perfused rat hearts, via mechanisms not involving myocardial ischemia during stretch. Less