title: Oxytocin protects cardiomyocytes from apoptosis induced by ischemia-reperfusion in rat heart: role of mitochondrial ATP-dependent potassium channel and permeability transition pore.
abstract: The current study examines the protective effect of oxytocin (OT) on cardiomyocyte apoptosis modulated by mitochondrial ATP-dependent potassium (mitoKATP) channel and permeability transition pore (mPTP) in the preconditioned myocardium of anesthetized rats. Eighty rats were equally divided into eight groups. The hearts of all animals except for the sham group were subjected to 25 min ischemia and 120 min reperfusion. Oxytocin, 5-hydroxydeconoate (5-HD), a specific inhibitor of the mitoKATP channel, and atractyloside (ATRC), an mPTP opener, were used prior to ischemia. Hemodynamic parameters were recorded throughout the experiment. Evaluations were made by infarct size, plasma lactate dehydrogenase level (LDH), transmission electron microscopy (TEM) and immunohistochemistry studies. OT prevented mean arterial pressure drop during early phase of ischemia and reperfusion. Treatment with OT before IR induction normalizes cardiomyocytes both in light microscopy and TEM observations. In addition, OT significantly reduced TUNEL- and increased Bcl-2-labeled positive cell number relative to IR (p<0.05). However, 5HD or ATRC inhibited the protective effects of OT on cardiomyocytes damaged by IR (p<0.05). Ultrastructural changes including extensive myofibril loss, sarcolemmal disruption and mitochondrial swelling due to amorphous dens bodies indicate necrosis induction in 5HD and ATRC as well as in IR groups. Restoration of immunohistochemistry parameters and protection against IR-induced ultrastructural changes confirm OT cardioprotective effects via mitoKATP channel and mPTP modulation in apoptosis induced by ischemia-reperfusion.
authors.affiliation: Cancer Research Center, Tehran University of Medical Science, Tehran, Iran.
authors.forename: Ali Mohammad
authors.initials: AM
authors.lastname: Alizadeh
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Faghihi
authors.forename: Vahid
authors.initials: V
authors.lastname: Khori
authors.forename: Hamid
authors.initials: H
authors.lastname: Sohanaki
authors.forename: Khalil
authors.initials: K
authors.lastname: Pourkhalili
authors.forename: Fahimeh
authors.initials: F
authors.lastname: Mohammadghasemi
authors.forename: Maryam
authors.initials: M
authors.lastname: Mohsenikia
mesh_terms: D000818:Animals; D017209:Apoptosis; D006439:Hemodynamics; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D046529:Microscopy, Electron, Transmission; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010121:Oxytocin / Q000494:pharmacology* / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D010121:Oxytocin; D007770:L-Lactate Dehydrogenase