KR-31761, a novel K+(ATP)-channel opener, exerts cardioprotective effects by opening both mitochondrial K+(ATP) and Sarcolemmal K+(ATP) channels in rat models of ischemia/reperfusion-induced heart injury.
KR-31761, a novel K+(ATP)-channel opener, exerts cardioprotective effects by opening both mitochondrial K+(ATP) and Sarcolemmal K+(ATP) channels in rat models of ischemia/reperfusion-induced heart injury.
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KR-31761 是一种新型 K (ATP) 通道开放剂，通过在缺血/再灌注诱发的心脏损伤大鼠模型中打开线粒体 K (ATP) 和肌膜 K (ATP) 通道来发挥心脏保护作用。
DOI：
10.1254/jphs.08132fp
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发表时间：
2009
影响因子：
3.5
通讯作者：
Hwa
中科院分区：
文献类型：
--
作者：
Min;Sung;H. Seo;K. Yi;S. Yoo;B. Lee;Hun;H. Won;Chang;S. Kwon;W. Choi;Hwa
在缺血/再灌注 (I/R) 心脏损伤大鼠模型中评估了新合成的 K+(ATP) 开启剂 KR-31761 的心脏保护作用。在经受 30 分钟整体缺血/30 分钟再灌注的离体大鼠心脏中，缺血前灌注 KR-31761 显着增加左心室发展压（药物前 LVDP 的百分比：对照组分别为 17.8、45.1、54.2 和 62.6，分别为 1 µM、3 µM 和 10 µM）和双乘积（DP：心率 x LVDP；药物前DP的百分比：在30分钟再灌注时，对照为17.5、44.9、56.2和64.5，分别为1μM、3μM和10μM，同时降低左心室舒张末压(LVEDP)。 KR-31761 (10 microM) 显着增加了缺血期间的挛缩时间，而它浓度依赖性地减少了再灌注期间乳酸脱氢酶的释放。所有这些参数均被线粒体 K+(ATP) (mitoK+(ATP)) 通道和 K+(ATP) 通道的选择性和非选择性阻断剂 5-羟基癸酸 (5-HD，100 µM) 和格列本脲 (1 µM) 显着逆转。在左冠状动脉前降支闭塞 30 分钟/2.5 小时再灌注的麻醉大鼠中，在缺血发作前 15 分钟施用 KR-31761 显着减少了梗塞面积（对照组为 72.2%、55.1% 和 47.1%，0.3 mg/kg，静脉注射和 1.0 mg/kg，静脉注射，分别）；在 KR-31761 之前 5 分钟给予 5-HD（10 mg/kg，静脉注射）和 HMR-1098（一种肌膜 K+(ATP) (sarcK+(ATP)) 通道选择性阻断剂（6 mg/kg，静脉注射））后，这些效应完全和几乎完全消除（分别为 72.3% 和 67.9%）。 KR-31761 仅略微松弛甲氧胺预收缩的大鼠主动脉（IC50：> 30.0 microM）。这些结果表明，KR-31761 通过打开大鼠心脏中的 mitoK+(ATP) 和 sarcK+(ATP) 通道发挥有效的心脏保护作用，同时具有最小的血管舒张作用。
The cardioprotective effects of KR-31761, 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/30-min reperfusion, KR-31761 perfused prior to ischemia significantly increased both the left ventricular developed pressure (% of predrug LVDP: 17.8, 45.1, 54.2, and 62.6 for the control, 1 microM, 3 microM, and 10 microM, respectively) and double product (DP: heart rate x LVDP; % of predrug DP: 17.5, 44.9, 56.2, and 64.5 for the control, 1 microM, 3 microM, and 10 microM, respectively) at 30-min reperfusion while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31761 (10 microM) significantly increased the time to contracture during the ischemic period, whereas it concentration-dependently decreased the lactate dehydrogenase release during reperfusion. All these parameters were significantly reversed by 5-hydroxydecanoate (5-HD, 100 microM) and glyburide (1 microM), selective and nonselective blockers of the mitochondrial K+(ATP) (mitoK+(ATP)) channel and K+(ATP) channel, respectively. In anesthetized rats subjected to 30-min occlusion of left anterior descending coronary artery/2.5-h reperfusion, KR-31761 administered 15 min before the onset of ischemia significantly decreased the infarct size (72.2%, 55.1%, and 47.1% for the control, 0.3 mg/kg, i.v., and 1.0 mg/kg, i.v., respectively); and these effects were completely and almost completely abolished by 5-HD (10 mg/kg, i.v.) and HMR-1098, a selective blocker of sarcolemmal K+(ATP) (sarcK+(ATP)) channel (6 mg/kg, i.v.) administered 5 min prior to KR-31761 (72.3% and 67.9%, respectively). KR-31761 only slightly relaxed methoxamine-precontracted rat aorta (IC50: > 30.0 microM). These results suggest that KR-31761 exerts potent cardioprotective effects through the opening of both mitoK+(ATP) and sarcK+(ATP) channels in rat hearts with a minimal vasorelaxant effect.
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BMS-191095 的药理学特征，它是一种线粒体 K(ATP) 开放剂，没有外周血管舒张剂或心脏动作电位缩短活性。
DOI：
--
发表时间：
2001
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Grover,GJ;D'Alonzo,AJ;Garlid,KD;Bajgar,R;Lodge,NJ;Sleph,PG;Darbenzio,RB;Hess,TA;Smith,MA;Paucek,P;Atwal,KS
通讯作者：
Atwal,KS
影响因子：
37.8
作者：
Liu, YG;Sato, T;Marban, E
通讯作者：
Marban, E
影响因子：
3.2
作者：
Mozaffari, Mahmood S.;Schaffer, Stephen W.
通讯作者：
Schaffer, Stephen W.
K(ATP) 通道开放剂产生急性和延迟心脏保护的机制。
DOI：
10.1016/j.vph.2005.02.008
发表时间：
2005
期刊：
Vascular pharmacology.
影响因子：
--
作者：
Wang,Yigang;Haider,HusnainKhawaja;Ahmad,Nauman;Ashraf,Muhammad
通讯作者：
Ashraf,Muhammad
DOI：
10.1152/ajpheart.00272.2006
发表时间：
2006-11-01
影响因子：
4.8
作者：
Andrukhiv, Anastasia;Costa, Alexandre D.;Garlid, Keith D.
通讯作者：
Garlid, Keith D.