title: Stimulation of Oxytocin Receptor during Early Reperfusion Period Protects the Heart against Ischemia/Reperfusion Injury: the Role of Mitochondrial ATP-Sensitive Potassium Channel, Nitric Oxide, and Prostaglandins.
abstract: 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, the 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, coronary effluent 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).
authors.affiliation: 1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Imani
authors.affiliation: 1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Khansari
authors.affiliation: Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Yaser
authors.initials: Y
authors.lastname: Azizi
authors.affiliation: 1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Kamran
authors.initials: K
authors.lastname: Rakhshan
authors.affiliation: 1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Faghihi
mesh_terms: D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000378:metabolism*; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D054086:KATP Channels; D010120:Oxytocics; D011453:Prostaglandins; D018045:Receptors, Oxytocin; C047046:atosiban; D009569:Nitric Oxide; D010121:Oxytocin; C052853:5-hydroxydecanoic acid; D014668:Vasotocin
keywords: Cyclooxygenase; Isolated heart; NO; Oxytocin; Postconditioning; mKATP