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Original Article

The Effect of Selective Endothelin Receptor a Antagonism by Bq-123 on Myocardial Ischemia-Reperfusion Induced Apoptotic Cell Death

Mehmet Cengiz Colak, Hakan Parlakpinar, Necip Ermis, Alaadin Polat, Cemil Colak, Bulent Mizrak, Ramazan Ozdemir, Ahmet Acet

   

Abstract
The objective of the present study was to investigate the possible impact of specific endothelin-A (ETA) receptor blockage by BQ-123 on myocardial ischemia-reperfusion (MI/R) induced apoptosis in rats. To produce MI/R, a branch of the descending left coronary artery was occluded for 30 min followed by 2 h reperfusion. Thirty-two rats were randomly assigned to four groups equally: (1) sham-operated group, (2) MI/R group, (3) MI/R+BQ-123-treated group, and (4) MI/R+ET-1+BQ-123-treated group. TUNEL staining, caspase-3 and caspase-9 activities were determined immunohistologically. MI/R group revealed extensive TUNEL positive cardiomyocytes especially in the free wall of the left ventricule, interventicular septum, and apex zone. Intensity of TUNEL-positive cardiomyocytes reduced as a result of BQ-123 treatment compared to the sham group in the same sections. Result of the caspase activity was found to correlate with TUNEL evaluation. BQ-123 administrations to MI/R group with or without ET-1 caused significant decrease both in lipid peroxidation and nitric oxide (NO) generation. Also, BQ-123 leads to augmentation of superoxide dismutase, catalase and glutathione contents. We propose that selective ETA antagonism by BQ-123 has a worthwhile effect on apoptotic cell death following MI/R, and that scavenging of free radicals by selective ETA antagonist is part of this beneficial effect.

Key words: Apoptosis, ETA receptor antagonist (BQ-123), endothelin; NO, reactive oxygen radicals, rat

Med-Science. 2012; 1(4): 254-70

 
Medicine Science Vol:1 Issue:4 Year:2012 PP:244-362
Posted in Vol: 1 Issue: 4 Year: 2012 December pp: 244-362

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