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KMID : 0043320080310040482
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Archives of Pharmacal Research
2008 Volume.31 No. 4 p.482 ~ p.489
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KR-31762, a Novel Channel Opener, Exerts Cardioprotective Effects by Opening Channels in Rat Models of Ischemia/reperfusion-induced Heart Injury
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Lee Sung-Hun
Lee Byung-Hoi
Shin Hwa-Sup
Yang Min-Kyu
Yi Kyu-Yang
Yoo Sung-Eun
Choi Wahn-Soo
Lee Chang-Soo
Won Hyung-Sik
Lim Jong-Hyun
Seo Ho-Won
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Abstract
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The cardioprotective effects of KR-31762, a newly synthesized 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 ) significantly increased the left ventricular developed pressure (LVDP) and double product (heart rate 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 , 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 ), a nonselective blocker of channel, but not by 5-hydroxydecanoate, a selective blocker of 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 (). These results suggest that KR-31762 exerts potent cardioprotective effects through the opening of sarcolemmal channel in rat hearts with the minimal vasorelaxant effects.
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KEYWORD
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KR-31762, Cardioprotection, Ischemia, Reperfusion, Rat heart
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