title: Oxidative stress mediates cardiac infarction aggravation induced by intermittent hypoxia.
abstract: We have previously shown that chronic intermittent hypoxia (IH), a component of the obstructive sleep apnea syndrome, increases heart sensitivity to infarction. We investigate here the deleterious mechanisms potentially involved in the IH-induced infarction aggravation, investigating the role of oxidative stress. Male Wistar rats were subjected to chronic IH or normoxia (N). IH consisted of repetitive 1-min cycles (30 s with inspired O2 fraction 5% followed by 30 s normoxia) and was applied for 8 h during daytime, for 14 days. After the 14-day exposure, mean arterial blood pressure (MABP) was higher in the hypoxic compared with the normoxic group. Infarct size, measured on isolated hearts after ischemia-reperfusion, was significantly increased in IH compared with normoxic group (36.0 ± 2.8% vs. 21.8 ± 3.1% for tempol corresponding control groups and 40.3 ± 3.5% vs. 29.4 ± 3.7% for melatonin corresponding control groups). Tempol or melatonin administration during the 14-day IH exposure prevented both IH-induced increase in MABP and infarction aggravation (24.8 ± 2.8% vs. 25.9 ± 4.0% for tempol-treated groups and 32.3 ± 3.2% vs. 34.5 ± 4.2% for melatonin-treated groups). Myocardial oxidative stress was induced by IH, as measured by dihydroethidium (DHE) level and p47-phox expression (the cytosolic protein required for the activation of the NADPH oxidase). This effect was abolished by tempol and melatonin treatments, which were able to normalize DHE level and NADPH expression. In conclusion, oxidative stress appears to mediate the deleterious cardiovascular effects of IH and, in particular, the increased myocardial susceptibility to infarction.
authors.affiliation: UJF, Laboratoire HP2, Grenoble F-38000, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Ramond
authors.forename: Diane
authors.initials: D
authors.lastname: Godin-Ribuot
authors.forename: Christophe
authors.initials: C
authors.lastname: Ribuot
authors.forename: Perle
authors.initials: P
authors.lastname: Totoson
authors.forename: Irina
authors.initials: I
authors.lastname: Koritchneva
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cachot
authors.forename: Patrick
authors.initials: P
authors.lastname: Levy
authors.forename: Marie
authors.initials: M
authors.lastname: Joyeux-Faure
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D062186:Arterial Pressure; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004996:Ethidium / Q000031:analogs & derivatives / Q000378:metabolism; D000860:Hypoxia / Q000150:complications*; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009249:NADP / Q000235:genetics; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; C067883:dihydroethidium; D009249:NADP; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D004996:Ethidium; D008550:Melatonin; C001803:tempol