title: Role of oxidative/nitrosative stress in the tolerance to ischemia/reperfusion injury in cardiomyopathic hamster heart.
abstract: We investigated the role of oxidative/nitrosative stress in the tolerance to ischemia/reperfusion (I/R) injury in BIO14.6 cardiomyopathy hamster hearts at 6 weeks of age. These hearts showed no significant morphologic change and left ventricular (LV) dysfunction. However, expression and activity of iNOS, nitrotyrosine (NT) formation, and protein kinase C (PKC)-epsilon activity were increased in these hearts. When the BIO14.6 hamster hearts were isolated and subjected to 40 min of global ischemia, they showed smaller myocardial necrosis and greater recovery of LV function during reperfusion compared with the control hamster heart. All of these effects were abrogated by prolonged treatment with the antioxidant, 2-mercaptopropionylglycine (MPG). Brief preischemic treatment with MPG or the iNOS inhibitor 1400W also abrogated NT formation and activation of PKC-epsilon and inhibited the tolerance to I/R injury in the BIO14.6 hamster heart. Brief preischemic treatment with the PKC inhibitor chelerythrine or the K(ATP) channel blockers, 5-hydroxydecanoate (5-HD) and glibenclamide, had no effect on iNOS activation and NT formation but inhibited the tolerance to I/R injury in the cardiomyopathic heart. These results suggest that oxidative/nitrosative stress plays a role in the tolerance to I/R injury in the cardiomyopathic heart through activation of PKC and the downstream effectors, K(ATP) channels.
authors.affiliation: Cardiovascular Center, Kansai Medical University, Moriguchi City, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Kyoi
authors.forename: Hajime
authors.initials: H
authors.lastname: Otani
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsuhisa
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Akita
authors.forename: Chiharu
authors.initials: C
authors.lastname: Enoki
authors.forename: Kimiko
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Reiji
authors.initials: R
authors.lastname: Hattori
authors.forename: Hiroji
authors.initials: H
authors.lastname: Imamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamihata
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
mesh_terms: D000470:Alkaloids; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D053119:Benzophenanthridines; D003402:Creatine Kinase / Q000378:metabolism; D006224:Cricetinae; D003652:Decanoic Acids / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D017202:Myocardial Ischemia / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000378:metabolism; D015538:Nitrosation; D018384:Oxidative Stress; D010617:Phenanthridines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D008625:Tiopronin / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D053119:Benzophenanthridines; D003652:Decanoic Acids; D004791:Enzyme Inhibitors; D006880:Hydroxy Acids; D010617:Phenanthridines; D026902:Potassium Channel Blockers; C002744:3-nitrotyrosine; D014443:Tyrosine; C052853:5-hydroxydecanoic acid; D008625:Tiopronin; C016299:chelerythrine; D052247:Nitric Oxide Synthase Type II; D051744:Protein Kinase C-epsilon; D003402:Creatine Kinase; D005905:Glyburide