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

1.本研究旨在探讨血管紧张素转换酶抑制剂替莫普利是否通过肌膜钾通道和/或线粒体钾通道直接保护心肌细胞免受缺氧/复氧损伤。将原代培养的新生大鼠心肌细胞暴露于低氧5小时，然后复氧2小时。通过乳酸脱氢酶(LD)的释放来评价心肌细胞的损伤程度。替莫普利显著抑制缺氧/复氧后LD的释放，并呈剂量依赖关系。吡那地尔和二氮嗪使LD释放量略有减少。格列本脲和5-羟基-癸酸不能减弱替莫普利对培养心肌细胞释放LD的心脏保护作用。我们的结果表明，血管紧张素转换酶抑制剂在抗缺氧/复氧损伤机制上不以K_1；ATP&gt；通道为靶点。2.本研究的目的是确定心肌牵张，w…心肌缺血后，由于左心室舒张末压(LVEDP)升高，K_1、K_(？)血流灌流的心脏先进行20min的全脑无血流缺血，然后再灌流30min。对照组LVEDP为10 mm Hg。牵张组在全脑缺血前将LVEDP升高至30或60 mm Hg，持续5min。全心缺血30min，再灌流30min。牵张组在全脑缺血前5分钟或15分钟将LVEDP升高至30或60毫米汞柱。30 mm Hg和60 mm Hg牵张组再灌注30min的血流动力学参数均有改善，30 mm Hg缓冲灌注组的血流动力学参数改善呈持续时间依赖性。增加LVEDP诱导的心肌牵张可通过牵张过程中不涉及心肌缺血的机制，对血液灌流和缓冲灌流的大鼠心脏进行预适应。较少

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