title: Dynamic changes in nitric oxide and mitochondrial oxidative stress with site-dependent differential tissue response during anoxic preconditioning in rat heart.
abstract: In this study, dynamic changes in nitric oxide (NO) and mitochondrial superoxide (O(2)(*-)) were examined during anoxic preconditioning (AP) in rat heart model. AP and anoxia-reoxygenation (A/R) were performed on isolated hearts and single cardiomyocytes. The cellular insult in the form of infarct size and DNA damage were localized and correlated with NO synthases (endothelial and inducible) expression levels. The results showed that endocardium was the most affected region in AP groups, whereas the larger area of infarct was confined to mid- and epicardium in the A/R group. Interestingly, a high-level expression of immunofluorescent NO synthases was restricted to viable areas in the AP. In contrast to the gradual increase in O(2)(*-) level that occurred in the AP group, a sudden massive increase in its level was demonstrated at the onset of reoxygenation in the A/R group. The observed increase in NO production during reoxygenation in the AP group was attenuated by inducible NO synthase inhibitor. The study revealed, on a real-time basis, the role played by preconditioning for modulating NO and O(2)(*-) levels on behalf of cell survival. The results afford a better understanding of cardiac-adapting mechanism during AP and the role of inducible NO synthase in this important phenomenon.
authors.affiliation: Mitochondrial Signaling Laboratory, Department of Physiology and Biophysics, College of Medicine, Mitochondrial Research Group-Frontier Inje Research Science and Technology Project, Inje University, Busanjin-Ku, Busan 614-735, Korea.
authors.forename: Dang Van
authors.initials: DV
authors.lastname: Cuong
authors.forename: Mohamad
authors.initials: M
authors.lastname: Warda
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Ko
authors.forename: Euiyong
authors.initials: E
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004272:DNA, Mitochondrial; D015221:Potassium Channels; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III