Özdemir, RamazanParlakpınar, HakanPolat, AlaadinÇolak, CemilErmiş, NecipAcet, Ahmet2018-01-122018-01-122006Özdemir, R., Parlakpınar, H., Polat, A., Çolak, C., Ermiş, N., & Acet, H. A. (2006). Selective Endothelin A Eta Receptor Antagonist Bq 123 Reduces Both Myocardial İnfarct Size And Oxidant İnjury. Toxicology, 219(1–3), 142–149.https://ac.els-cdn.com/S0300483X05005597/1-s2.0-S0300483X05005597-main.pdf?_tid=e00295a8-f762-11e7-9719-00000aacb35e&acdnat=1515739158_c1b917b4a7e91ee1c4f83f3d2556f729https://hdl.handle.net/11616/7978Toxicology 219 (2006) 142–149.Objective: Endothelins (ET) can be considered stress-responsive regulators working in paracrine and autocrine fashion. It has been suggested that elevated levels of ET may be responsible for the low coronary re-flow phenomena. Ischemia–reperfusion (I/R) was shown to stimulate ET release in rat heart; however, the mechanism(s) of this effect has not been clarified. Therefore, this study was focused to investigate the effect of BQ-123, selective ETA receptor antagonist, on three aspects of myocardial ischemia–reperfusion (MI/R) injury: hemodynamic parameters, infarct size and oxidant–antioxidant status in the absence and presence of ET-1 in an vivo rat model. Methods and results: To produce MI/R, a branch of the descending left coronary artery was occluded for 30 min followed by 2 h reperfusion. ECG changes, blood pressure (BP), and heart rate (HR) were measured before occlusion and continued both occlusion and reperfusion. Forty rats were randomly assigned to five groups equally: (1) sham-operated rats without coronary ligation, (2) I/R group, (3) I/R + BQ-123-treated group (10 g/kg/min i.v.), (4) I/R + ET-treated group (25 ng/kg/min i.v.), (5) I/R + ET + BQ123-treated group. The results are expressed as mean ± S.E.M. In the ET-1 plus I/R group, the ratio between the infarcted area and area at risk 56 ± 1% was significantly higher than I/R group (49 ± 1%). In the BQ-123 group with or without exogenous ET-1 treatment in I/R group, this ratio was significantly lower at 40 ± 2 and 37 ± 1%, respectively. As compared to sham group, I/R increased lipid peroxidation whereas decreased nitric oxide (NO), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) contents. This decreased antioxidant enzymatic defense could result in aggravated oxidative damage in I/R group rat hearts. ET-1 administration group showed severe oxidative damage. BQ-123 administrations to I/R group with or without ET-1 caused significantly decrease in lipid peroxidation and increased in SOD, CAT activities and NO generation and GSH content when compared with I/R group alone. Conclusions: The most important finding of the present study is that the ET blockade reduced I/R-induced myocardial injury. The mechanism of this reduction was speculated to be a resistance to ischemic injury in the subcellular levels of the myocardium conferred by a reduction of vascular constriction and improvement of imbalance in the antioxidant status. © 2005 Elsevier Ireland Ltd. All rights reserved.eninfo:eu-repo/semantics/openAccessETA receptor antagonist (BQ-123)EndothelinReactive oxygen radicalsRatArticle129(1-3)142149