title: Metabolic and cardiac signaling effects of inhaled hydrogen sulfide and low oxygen in male rats.
abstract: Low concentrations of inhaled hydrogen sulfide (H(2)S) induce hypometabolism in mice. Biological effects of H(2)S in in vitro systems are augmented by lowering O(2) tension. Based on this, we hypothesized that reduced O(2) tension would increase H(2)S-mediated hypometabolism in vivo. To test this, male Sprague-Dawley rats were exposed to 80 ppm H(2)S at 21% O(2) or 10.5% O(2) for 6 h followed by 1 h recovery at room air. Rats exposed to H(2)S in 10.5% O(2) had significantly decreased body temperature and respiration compared with preexposure levels. Heart rate was decreased by H(2)S administered under both O(2) levels and did not return to preexposure levels after 1 h recovery. Inhaled H(2)S caused epithelial exfoliation in the lungs and increased plasma creatine kinase-MB activity. The effect of inhaled H(2)S on prosurvival signaling was also measured in heart and liver. H(2)S in 21% O(2) increased Akt-P(Ser473) and GSK-3β-P(Ser9) in the heart whereas phosphorylation was decreased by H(2)S in 10.5% O(2), indicating O(2) dependence in regulating cardiac signaling pathways. Inhaled H(2)S and low O(2) had no effect on liver Akt. In summary, we found that lower O(2) was needed for H(2)S-dependent hypometabolism in rats compared with previous findings in mice. This highlights the possibility of species differences in physiological responses to H(2)S. Inhaled H(2)S exposure also caused tissue injury to the lung and heart, which raises concerns about the therapeutic safety of inhaled H(2)S. In conclusion, these findings demonstrate the importance of O(2) in influencing physiological and signaling effects of H(2)S in mammalian systems.
authors.affiliation: Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Asaf
authors.initials: A
authors.lastname: Stein
authors.forename: Zhengkuan
authors.initials: Z
authors.lastname: Mao
authors.forename: Joanna P
authors.initials: JP
authors.lastname: Morrison
authors.forename: Michelle V
authors.initials: MV
authors.lastname: Fanucchi
authors.forename: Edward M
authors.initials: EM
authors.lastname: Postlethwait
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
authors.forename: David W
authors.initials: DW
authors.lastname: Kraus
authors.forename: Jeannette E
authors.initials: JE
authors.lastname: Doeller
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Bailey
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D052279:Creatine Kinase, MB Form / Q000097:blood; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006339:Heart Rate / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000008:administration & dosage* / Q000633:toxicity; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012694:Serine; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D012694:Serine; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D052279:Creatine Kinase, MB Form; D010100:Oxygen; D006862:Hydrogen Sulfide