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The Safe Pathway Is Involved in the Postconditioning Mechanism of Oxytocin in Isolated Rat Heart Publisher Pubmed



Polshekan M1, 2 ; Khori V1 ; Alizadeh AM3, 4 ; Ghayourmobarhan M5 ; Saeidi M6 ; Jand Y1 ; Rajaei M1 ; Farnoosh G7 ; Jamialahmadi K8, 9
Authors
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Authors Affiliations
  1. 1. Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
  2. 2. Student Research Committee, Department of Modern Science and Technology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  3. 3. Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Metabolic Syndrome Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  6. 6. Stem cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran
  7. 7. Applied Biotechnology Research Centre, Baqiyatallah University of Medical Sciences, Tehran, Iran
  8. 8. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  9. 9. Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Source: Peptides Published:2019


Abstract

Oxytocin (OT) has a postconditioning effect against the ischemia-reperfusion (I/R) injury. However, its precise cardioprotection mechanism at the early reperfusion phase remains under debate. Our previous study revealed that OT postconditioning (OTpost) is cardioprotective by activating the Reperfusion Injury Salvage Kinase (RISK) pathway. Therefore, the present study is aimed to determine the biological effects of OTpost via the OT receptor and the activation of the JAK/STAT3 signaling pathway, mitochondrial adenosine triphosphate-dependent potassium channel (mitoKATP), nitric oxide (NO) release, and its anti-apoptotic effects against I/R injury in an isolated rat heart model. Sixty-three rats were randomly allocated to one of nine groups. OT was perfused 40 min prior to the regional ischemia or 15 min at the early reperfusion phase. AG490 (a JAK/STAT3 inhibitor), 5HD (a mitoKATP blocker), atosiban (an OT receptor antagonist), L-NAME (a nonspecific nitric oxide synthase inhibitor) were applied either alone or in combination with OT during the pre-ischemia phase and/or in the early reperfusion phase. Myocardial infarct size, hemodynamic factor, ventricular arrhythmia, coronary flow, cardiac biochemical marker, and the apoptosis index were determined at the end of reperfusion. Oxytocin postconditioning reduced infarct size, lactate dehydrogenase activity, arrhythmia score, ventricular fibrillation, and apoptosis. Moreover, AG490, 5HD, atosiban, and L-NAME abrogated the cardioprotective effects of OT. Our results demonstrated that the cardioprotective effects of OT are mediated by NO release, and the activation of mitoKATP and the SAFE pathway through the JAK/STAT3 signaling cascade that finally lead to decrease in the apoptosis index during the early reperfusion phase. © 2018 Elsevier Inc.