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KR-31762, a Novel $K_{ATP}$ Channel Opener, Exerts Cardioprotective Effects by Opening $SarcK_{ATP}$ Channels in Rat Models of Ischemia/reperfusion-induced Heart Injury
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  • KR-31762, a Novel $K_{ATP}$ Channel Opener, Exerts Cardioprotective Effects by Opening $SarcK_{ATP}$ Channels in Rat Models of Ischemia/reperfusion-induced Heart Injury
  • KR-31762, a Novel $K_{ATP}$ Channel Opener, Exerts Cardioprotective Effects by Opening $SarcK_{ATP}$ Channels in Rat Models of Ischemia/reperfusion-induced Heart Injury
저자명
Lee. Sung-Hun,Yang. Min-Kyu,Lim. Jong-Hyun,Seo. Ho-Won,Yi. Kyu-Yang,Yoo. Sung-Eun,Lee. Byung-Ho,Won. Hyung-Sik,Lee. Chang-Soo,Ch
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2008년|31권 4호|pp.482-489 (8 pages)
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대한약학회
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정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
서지반출

기타언어초록

The cardioprotective effects of KR-31762, a newly synthesized $K^+_{ATP}$ opener, were evaluated in rat models of ischemia/reperfusion (I/R) heart injury. In isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, KR-31762 (3 and 10 ${mu}M$) significantly increased the left ventricular developed pressure (LVDP) and double product (heart rate ${ imes}$ LVDP) after 30-min referfusion in a concentration-dependent manner, while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31762 also significantly increased the time to contracture (TIC) during ischemic period (20.0, 22.4 and 26.4 min for control, 3 and 10 ${mu}M$, respectively), while decreasing the release of lactate dehydrogenase (LDH) from the heart during 30 min reperfusion (30.4, 14.3 and 19.7 U/g heart weight, respectively). All these parameters except LDH release were reversed by glyburide (1 ${mu}M$), a nonselective blocker of $K^+_{ATP}$ channel, but not by 5-hydroxydecanoate, a selective blocker of $mitoK^+_{ATP}$ channel. In anesthetized rats subjected to 45-min occlusion of left anterior descending coronary artery followed by 90-min reperfusion, KR-31762 significantly decreased the infarct size (60.8, 40.5 and 37.8% for control, 0.3 and 1.0 mg/kg, iv, respectively). KR-31762 slightly relaxed the isolated rat aorta precontracted with methoxamine ($IC_{50}:;23.5;{mu}M$). These results suggest that KR-31762 exerts potent cardioprotective effects through the opening of sarcolemmal $K_{ATP}$ channel in rat hearts with the minimal vasorelaxant effects.