title: Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice.
abstract: Obstructive sleep apnea is associated with increased risk for cardiovascular diseases. As obstructive sleep apnea is characterized by episodic cycles of hypoxia and normoxia during sleep, we investigated effects of intermittent hypoxia (IH) on ischemia-reperfusion-induced myocardial injury. C57BL/6 mice were subjected to IH (2 min 6% O(2) and 2 min 21% O(2)) for 8 h/day for 1, 2, or 4 wk; isolated hearts were then subjected to ischemia-reperfusion. IH for 1 or 2 wk significantly enhanced ischemia-reperfusion-induced myocardial injury. However, enhanced cardiac damage was not seen in mice treated with 4 wk of IH, suggesting that the heart has adapted to chronic IH. Ischemia-reperfusion-induced lipid peroxidation and protein carbonylation were enhanced with 2 wk of IH, while, with 4 wk, oxidative stress was normalized to levels in animals without IH. H(2)O(2) scavenging activity in adapted hearts was higher after ischemia-reperfusion, suggesting the increased antioxidant capacity. This might be due to the involvement of thioredoxin, as the expression level of this protein was increased, while levels of other antioxidant enzymes were unchanged. In the heart from mice treated with 2 wk of IH, ischemia-reperfusion was found to decrease thioredoxin. Ischemia-reperfusion injury can also be enhanced when thioredoxin reductase was inhibited in control hearts. These results demonstrate that IH changes the susceptibility of the heart to oxidative stress in part via alteration of thioredoxin.
authors.affiliation: Dept. of Pharmacology, Georgetown University Medical Center, Washington, DC 20057, USA. ys82@georgetown.edu
authors.forename: Ah-Mee
authors.initials: AM
authors.lastname: Park
authors.forename: Yuichiro J
authors.initials: YJ
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050991:GATA4 Transcription Factor / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D050050:Protein Carbonylation; D020181:Sleep Apnea, Obstructive / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D013997:Time Factors; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494812:Bcl2l1 protein, mouse; D004137:Dinitrochlorobenzene; D004791:Enzyme Inhibitors; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D051020:bcl-X Protein; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D013880:Thioredoxin-Disulfide Reductase