首页> 美国卫生研究院文献>British Journal of Pharmacology and Chemotherapy >Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan a mixed ETA-ETB antagonist.
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Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan a mixed ETA-ETB antagonist.

机译:内源性内皮素在大鼠缺血和再灌注后心肌和冠状动脉内皮损伤中的作用:用波生坦(一种ETA-ETB混合拮抗剂)进行的研究。

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摘要

1. Previous studies suggested that endothelin-1 (ET-1) may play a role in myocardial ischaemia and reperfusion. This study was designed to test the effect of a new nonpeptide antagonist of endothelin ETA and ETB receptors, bosentan, on myocardial infarct size, ventricular arrhythmias, and coronary endothelial dysfunction after ischaemia and reperfusion. 2. Anaesthetized male Wistar rats were subjected to 20 min ischaemia (left coronary artery occlusion) followed by 1 h (for the evaluation of coronary endothelial dysfunction) or 2 h (for the evaluation of infarct size) reperfusion, or 5 min ischaemia followed by 15 min reperfusion (for the evaluation of reperfusion arrhythmias). Vascular studies were performed on 1.5-2 mm coronary segments (internal diameter 250-300 microns) removed distal to the site of occlusion and mounted in wire myographs for isometric tension recording. Area at risk and infarct size were determined by Indian ink injection and triphenyl tetrazolium staining, using computerized analysis of enlarged sections after colour video acquisition. 3. Bosentan, administered at a dose which virtually abolished the pressor response to big ET-1 (3 mg kg-1, i.v. before ischaemia) did not affect heart rate, arterial pressure or the rate pressure product before ischaemia, during ischaemia and during reperfusion. Bosentan did not affect the incidence of reperfusion-induced ventricular fibrillation (controls: 86%, n = 14; bosentan: 93%, n = 15), and did not modify infarct size (% of area at risk: controls: 63 +/- 4, n = 10; bosentan: 60 +/- 6, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)
机译:1.先前的研究表明内皮素-1(ET-1)可能在心肌缺血和再灌注中起作用。这项研究旨在测试新型的内皮素ETA和ETB受体非肽拮抗剂波生坦对缺血和再灌注后心肌梗死面积,室性心律失常和冠状动脉内皮功能障碍的影响。 2.麻醉的雄性Wistar大鼠先进行20分钟局部缺血(左冠状动脉闭塞),然后再进行1小时(用于评估冠状动脉内皮功能障碍)或2小时(用于评估梗死面积)再灌注,或进行5分钟局部缺血15分钟再灌注(用于评估再灌注心律不齐)。对1.5-2 mm冠状动脉节段(内径250-300微米)进行了血管研究,该节段从阻塞部位的远端移开,并安装在钢丝肌电图仪中,用于等距张力记录。通过彩色墨水采集后放大部分的计算机分析,通过印度墨水注射和三苯基四唑鎓染色确定高危区域和梗塞面积。 3. Bosentan的剂量实际上消除了对大ET-1的升压反应(3 mg kg-1,在缺血前静脉注射),不会影响心律,动脉压或缺血前,缺血期间和期间的速率乘积。再灌注。波生坦未影响再灌注诱导的心室纤颤的发生率(对照组:86%,n = 14;波生坦:93%,n = 15),并且未改变梗塞面积(危险区域的百分比:对照组:63 + / -4,n = 10;波生坦:60 +/- 6,n = 8)(抽象截断为250字)

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