|Title:||Differential Effects of Sarcolmmal and Mitochondrial Katp Channels Activated by 17β-Estradial on Reperfusion Arrhythmias and Infarct Sizes in Canine Heartd||Authors:||TSAI, CHANG-HER
|Keywords:||VENTRICULAR-FIBRILLATION;MYOCARDIAL-INFARCTION;CORONARY- OCCLUSION;ISCHEMIA;RAT;MYOCYTES||Issue Date:||2002||Journal Volume:||v.301||Journal Issue:||n.1||Start page/Pages:||23-4||Source:||JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS||Abstract:||
We have demonstrated the effects of estrogen on modulation of ATP- sensitive K+ channels; however, the subcellular location of these channels is unknown. The purpose of the present study was to investigate the role of the sarcolmmal and mitochondrial ATP-sensitive K+ channels in a canine model of myocardial infaraction after stimulation with 17β- esreadial. Anesthetized dogs were subjected to 60 min of the left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Infarct size was markedly reduced in estradial-treated dog compared with controls (14± 6 versus 42 ±6 %, p < 0.0001), indication the effective dose of estradial administrated. Pretreatment with the mitochondrial ATP-sensitive K+ channel antagonist 5- hydroxydecanoate completely abolished estradial- induced cardioprotection. The sarcolemmal ATP-sensitive K+ channel antagonist 1-15-12-(5- chloro-o-anisamido) ethylmjethoxypheny) sulfonyl-3- methylthiourea (HMR 1098) did not significantly attenuate estradial- induecd infarct size limitation. in addition, estradial administration significantly reduced the incidence and duration of reperfusion-induced ventricular tachycardia and ventricular fibrillation. Although 5- hydroxydecanoate alone caused no sigificant effect on the incidence of reperfusion arrhythmias in the presence or absence of estradial, the administration of HMR 1098 abolished estrogen-in-duced improvment of reperfusion arrhythmias. Pretreatment with the estrogen-receptor antagonist faslodex(ICI 182, 780)did not alter estrogen-induced infarct- limiting and antiarrhythmic effects. These results demonstrate that estrogen is cardioprotective against infarct size and fatal reperfusion arrhythmias by different ATP-sensitive K+ channels for an estrogen receptor- independent mechanism. The infarct size- limiting and antiarrhythmic effects of estrogen were abolished by 5- hydroxydecanoate and HMR 1098, Suggesting that the effects may result from activation of the mitochondial and sarcolemmal ATP-sensitive K+ channels, respectively.
|Appears in Collections:||醫學系|
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