title: Cardioprotective and nonprotective regimens of chronic hypoxia diversely affect the myocardial antioxidant systems.
abstract: It has been documented that adaptation to hypoxia increases myocardial tolerance to ischemia-reperfusion (I/R) injury depending on the regimen of adaptation. Reactive oxygen species (ROS) formed during hypoxia play an important role in the induction of protective cardiac phenotype. On the other hand, the excess of ROS can contribute to tissue damage caused by I/R. Here we investigated the relationship between myocardial tolerance to I/R injury and transcription activity of major antioxidant genes, transcription factors, and oxidative stress in three different regimens of chronic hypoxia. Adult male Wistar rats were exposed to continuous normobaric hypoxia (FiO2 0.1) either continuously (CNH) or intermittently for 8 h/day (INH8) or 23 h/day (INH23) for 3 wk period. A control group was kept in room air. Myocardial infarct size was assessed in anesthetized open-chest animals subjected to 20 min coronary artery occlusion and 3 h reperfusion. Levels of mRNA transcripts and the ratio of reduced and oxidized glutathione (GSH/GSSG) were analyzed by real-time RT-PCR and by liquid chromatography, respectively. Whereas CNH as well as INH8 decreased infarct size, 1 h daily reoxygenation (INH23) abolished the cardioprotective effect and decreased GSH/GSSG ratio. The majority of mRNAs of antioxidant genes related to mitochondrial antioxidant defense (manganese superoxide dismutase, glutathione reductase, thioredoxin/thioredoxin reductase, and peroxiredoxin 2) were upregulated in both cardioprotective regimens (CNH, INH8). In contrast, INH23 increased only PRX5, which was not sufficient to induce the cardioprotective phenotype. Our results suggest that the increased mitochondrial antioxidant defense plays an important role in cardioprotection afforded by chronic hypoxia.
authors.affiliation: Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic;
authors.forename: Dita
authors.initials: D
authors.lastname: Kasparova
authors.affiliation: Institute of Physiology, The Czech Academy of Sciences, Prague, Czech Republic; and.
authors.forename: Jan
authors.initials: J
authors.lastname: Neckar
authors.affiliation: National Institute of Public Health, Prague, Czech Republic.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Dabrowska
authors.affiliation: Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic;
authors.forename: Jiri
authors.initials: J
authors.lastname: Novotny
authors.affiliation: National Institute of Public Health, Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Mraz
authors.affiliation: Institute of Physiology, The Czech Academy of Sciences, Prague, Czech Republic; and.
authors.forename: Frantisek
authors.initials: F
authors.lastname: Kolar
authors.affiliation: Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic; jitka.zurmanova@natur.cuni.cz.
authors.forename: Jitka
authors.initials: J
authors.lastname: Zurmanova
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002853:Chromatography, Liquid; D005980:Glutathione Reductase / Q000235:genetics; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D054464:Peroxiredoxins / Q000235:genetics; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D000975:Antioxidants; D054464:Peroxiredoxins; D013482:Superoxide Dismutase; D005980:Glutathione Reductase
keywords: adaptation to hypoxia; antioxidant defense; cardioprotection; ischemia-reperfusion injury; oxidative stress