Contribution of mitochondrial K_<ATP> channel to cardioprotection against hypoxia or ischemia in rat cultured myocytes and isolated blood-perfused hearts
| Project/Area Number |
13670756
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
ASAYAMA Jun Kyoto Pharmaceutical University, Dept. of Pharmacology, Professor, 薬学部, 教授 (60079796)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Cultured myocyte / mitochondrial K_<ATP> channel / reperfusion injury / reoxygenation injury / myocardial stretch / ACE-inhibitor / 心筋アポトーシス / IL-1β / ACE-I |
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| Research Abstract |
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
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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
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Report
(3 results)
Research Products
(1 results)
