Bosentan, the mixed ET_A–ET_B endothelin receptor antagonist, attenuated oxidative stress after experimental myocardial ischemia and reperfusion

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• 作者：Suresh K. Gupta ; Amit Saxena ; Uma Singh and Dharamvir S. Arya
• 关键词：bosentan ; cardioprotection ; endothelin ; myocardial ischemia ; reperfusion ; oxidative stress
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2005
• 出版时间：July 2005
• 年：2005
• 卷：275
• 期：1-2
• 页码：67-74
• 全文大小：188 KB

文摘

Endothelin-1 has been shown to be associated with greater myocardial ischemia and reperfusion injury in which oxidative stress plays a key role. The efficacy of bosentan, a mixed ET_A–ET_B endothelin receptor antagonist, in protecting the myocardium from ischemia-reperfusion injury and oxidative stress was studied in open-chest Wistar rats. Anesthetized adult male rats (175–250 g b wt) underwent sham operation (SHAM group) or were subjected to 40 min of myocardial ischemia (MI) induced by temporary occlusion of the left anterior descending coronary artery (LAD) followed by 2 h reperfusion (R). Rats submitted to the MI-R protocol were administered bosentan at a dose of 3 mg/kg i.v. 20 min (BOS group) or saline (CON group) 20 min post-occlusion of LAD. After the 2 h reperfusion period the animals were euthanized and the heart rapidly excised. Cardiac tissue samples were snap frozen in liquid nitrogen for biochemical assay and were fixed in 10 % formalin solution for histologic evaluation. Myocardial I-R resulted in a significant increase (p p p p p These results are consistent with the concept that endothelin-1 may be involved in the pathogenesis of myocardial ischemia and infarction. This study demonstrates the antioxidant effect of non-selective endothelin receptor antagonism elucidating that, part of the aetiology of ischemia and reperfusion induced myocardial injury involves impaired antioxidant defenses.