title: Oxytocin protects rat heart against ischemia-reperfusion injury via pathway involving mitochondrial ATP-dependent potassium channel.
abstract: Cardiac preconditioning represents the most potent and consistently reproducible method of rescuing heart tissue from undergoing irreversible ischemic damage. One of the major goals of the current cardiovascular research is to identify a reliable cardioprotective intervention that can salvage ischemic myocardium. The aim of the present study is to evaluate the oxytocin (OT)-induced cardioprotection and the signaling pathway involved with mitochondrial ATP-dependent potassium (mitoKATP) channel in the anesthetized rat heart. Animals were divided into six groups (n=6): (1) IR; hearts were subjected to 25 min ischemia and 120 min reperfusion, (2) OT; oxytocin was administered (0.03 microg/kg i.p.) 25 min prior to ischemia, (3) ATO+OT; atosiban (ATO) was used as an OT-selective receptor antagonist (1.5 microg/kg i.p.) 10 min prior to OT administration, (4) ATO; atosiban was used 35 min prior to ischemia, (5) 5HD+OT; 5-hydroxydecanoic acid (5HD) was used as a specific inhibitor of mitoKATP channel (10mg/kg i.v.) 10 min prior to OT administration, (6) 5HD; 5HD was used 35min prior to ischemia. Then infarct size, ventricular arrhythmia and creatine kinase-MB isoenzyme (CK-MB) plasma level were measured. Hemodynamic parameters were recorded throughout the experiment. OT administration significantly decreased infarct size, CK-MB plasma level, severity and incidence of ventricular arrhythmia as compared to IR group. Administration of atosiban and 5HD abolished the cardiopreconditioning effect of OT. This study demonstrates that cardioprotective effects of OT are mediated through opening the mitoKATP channels.
authors.affiliation: Department of Physiology, School of Medicine, Tehran University of Medical Science, Enghelab Ave, Enghelab Squ, Tehran, Islamic Republic of Iran.
authors.forename: Ali Mohammad
authors.initials: AM
authors.lastname: Alizadeh
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Faghihi
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Sadeghipour
authors.forename: Fahimeh
authors.initials: F
authors.lastname: Mohammadghasemi
authors.forename: Alireza
authors.initials: A
authors.lastname: Imani
authors.forename: Fariba
authors.initials: F
authors.lastname: Houshmand
authors.forename: Vahid
authors.initials: V
authors.lastname: Khori
mesh_terms: D000818:Animals; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010121:Oxytocin / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D010121:Oxytocin