title: Inhalation of hydrogen gas attenuates left ventricular remodeling induced by intermittent hypoxia in mice.
abstract: Sleep apnea syndrome increases the risk of cardiovascular morbidity and mortality. We previously reported that intermittent hypoxia increases superoxide production in a manner dependent on nicotinamide adenine dinucleotide phosphate and accelerates adverse left ventricular (LV) remodeling. Recent studies have suggested that hydrogen (H(2)) may have an antioxidant effect by reducing hydroxyl radicals. In this study, we investigated the effects of H(2) gas inhalation on lipid metabolism and LV remodeling induced by intermittent hypoxia in mice. Male C57BL/6J mice (n = 62) were exposed to intermittent hypoxia (repetitive cycle of 1-min periods of 5 and 21% oxygen for 8 h during daytime) for 7 days. H(2) gas (1.3 vol/100 vol) was given either at the time of reoxygenation, during hypoxic conditions, or throughout the experimental period. Mice kept under normoxic conditions served as controls (n = 13). Intermittent hypoxia significantly increased plasma levels of low- and very low-density cholesterol and the amount of 4-hydroxy-2-nonenal-modified protein adducts in the LV myocardium. It also upregulated mRNA expression of tissue necrosis factor-α, interleukin-6, and brain natriuretic peptide, increased production of superoxide, and induced cardiomyocyte hypertrophy, nuclear deformity, mitochondrial degeneration, and interstitial fibrosis. H(2) gas inhalation significantly suppressed these changes induced by intermittent hypoxia. In particular, H(2) gas inhaled at the timing of reoxygenation or throughout the experiment was effective in preventing dyslipidemia and suppressing superoxide production in the LV myocardium. These results suggest that inhalation of H(2) gas was effective for reducing oxidative stress and preventing LV remodeling induced by intermittent hypoxia relevant to sleep apnea.
authors.affiliation: Faculty of Medicine, Department of Internal Medicine III, Osaka Medical College, Takatsuki, Osaka, Japan. in3015@poh.osaka-med.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Miyamura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Mori
authors.forename: Akira
authors.initials: A
authors.lastname: Ukimura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Ishizaka
mesh_terms: D000280:Administration, Inhalation; D000447:Aldehydes / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005355:Fibrosis; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D005740:Gases; D005786:Gene Expression Regulation; D006331:Heart Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006859:Hydrogen / Q000008:administration & dosage*; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015850:Interleukin-6 / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000447:Aldehydes; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D016166:Free Radical Scavengers; D005740:Gases; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D020097:Natriuretic Peptide, Brain; D006859:Hydrogen; C027576:4-hydroxy-2-nonenal