Phenylephrine induces early and late cardioprotection through mitochondrial permeability transition pore in the isolated rat heart.
BACKGROUND
The aim of this study was to investigate the role of mitochondrial permeability transition pore (mPTP) in cardioprotection afforded by phenylephrine pretreatment in early and late phases.


METHODS
Rat hearts were isolated and perfused with Krebs buffer in Langendorff preparation and subjected to 30 min regional ischemia followed by 60 min of reperfusion. Phenylephrine as a selective α1-adrenoceptor agonist and atractyloside as a specific opener of the mPTP were used. Seven groups (n = 6) of rats were randomly studied: (I) control: surgical procedure was performed with no ischemia/reperfusion, (II) ischemia/reperfusion: hearts underwent regional ischemia/reperfusion, (III) early phenylephrine: phenylephrine (50 μM) was perfused for 5 min prior to ischemia/reperfusion, (IV) late phenylephrine: rats were treated with phenylephrine (10 mg/kg, i.p) 24 h prior to ischemia/reperfusion, (V) early phenylephrine+atractyloside: hearts were perfused with phenylephrine as in group III and then atractyloside (20 mM) 5 min before reperfusion for 20 min, (VI) late phenylephrine+atractyloside: hearts were treated with phenylephrine as in group IV and then received atractyloside (20 mM), 5 min before reperfusion for 20 min, (VII) atractyloside-IR group: hearts were perfused with atractyloside (20 mM) 5 min before reperfusion for 20 min.


RESULTS
Compared with ischemia/reperfusion group, perfusion of phenylephrine in early and late phases decreased myocardial infarct size (% of ischemia zone), reduced creatine kinase-MB (CK-MB) in the coronary effluent, and improved cardiac function. Administration of atractyloside abolished cardioprotective effects of phenylephrine in both early and late phases and returned infarct size, CK-MB and cardiac function to levels as seen in ischemia/reperfusion group.


CONCLUSIONS
These results suggest that administration of atractyloside as a specific opener of the mPTP abolishes phenylephrine-induced early and late cardioprotection in the isolated rat hearts.
Naderi
Roya
R
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Imani
Alireza
A
Faghihi
Mahdieh
M
Moghimian
Maryam
M
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D052279:Creatine Kinase, MB Form / Q000097:blood; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology
D002316:Cardiotonic Agents; D010656:Phenylephrine; D052279:Creatine Kinase, MB Form