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

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.