Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 53 8 2015 10 06 491 500 EN Alireza Imani 1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Maryam Khansari 1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Yaser Azizi Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Kamran Rakhshan 1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Mahdieh Faghihi 1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2015 10 06 2015 10 06 Postconditioning is a simple and safe strategy for cardioprotection and infarct size limitation. Our previous study showed that oxytocin (OT) exerts postconditioning effect on ischemic/reperfused isolated rat heart. The aim of this study was to investigate the involvement of OT receptor, mitochondrial ATP-sensitive potassium channel (mKATP), nitric oxide (NO) and cyclooxygenase (COX) pathways in OT postconditioning. Isolated rat hearts were divided into10 groups and underwent 30 min of regional ischemia followed by 120 min of reperfusion (n =6). In I/R (ischemia/reperfusion) group, ischemia and reperfusion were induced without any treatment. In OT group, oxytocin was perfused 5 min prior to beginning of reperfusion for 25 min. In groups 3-6, atosiban (oxytocin receptor blocker), L-NAME (N-Nitro-L-Arginine Methyl Ester, non-specific nitric oxide synthase inhibitor), 5-HD (5-hydroxydecanoate, mKATP inhibitor) and indomethacin (cyclooxygenase inhibitor) were infused prior to oxytocin administration. In others,  he mentioned inhibitors were perfused prior to ischemia without oxytocin infusion. Infarct size, ventricular hemodynamic, coronary effluent, malondialdehyde (MDA) and lactate dehydrogenase (LDH) were measured at the end of reperfusion. OT perfusion significantly reduced infarct size, MDA and LDH in comparison with IR group. Atosiban, 5HD, L-NAME and indomethacin abolished the postconditioning effect of OT. Perfusion of the inhibitors alone prior to ischemia had no effect on infarct size, hemodynamic parameters, coronaryeffluent and biochemical markers as compared with I/R group. In conclusion, this study indicates that postconditioning effects of OT are mediated by activation of mKATP and production of NO and Prostaglandins (PGs). https://acta.tums.ac.ir/index.php/acta/article/view/4275 https://acta.tums.ac.ir/index.php/acta/article/download/4275/4230