Metabolic and cardiac signaling effects of inhaled hydrogen sulfide and low oxygen in male rats

Abstract

Low concentrations of inhaled hydrogen sulfide (H2S) induce hypometabolism in mice. Biological effects of H2S in in vitro systems are augmented by lowering O2tension. Based on this, we hypothesized that reduced O2tension would increase H2S-mediated hypometabolism in vivo. To test this, male Sprague-Dawley rats were exposed to 80 ppm H2S at 21% O2or 10.5% O2for 6 h followed by 1 h recovery at room air. Rats exposed to H2S in 10.5% O2had significantly decreased body temperature and respiration compared with preexposure levels. Heart rate was decreased by H2S administered under both O2levels and did not return to preexposure levels after 1 h recovery. Inhaled H2S caused epithelial exfoliation in the lungs and increased plasma creatine kinase-MB activity. The effect of inhaled H2S on prosurvival signaling was also measured in heart and liver. H2S in 21% O2increased Akt-PSer473and GSK-3β-PSer9in the heart whereas phosphorylation was decreased by H2S in 10.5% O2, indicating O2dependence in regulating cardiac signaling pathways. Inhaled H2S and low O2had no effect on liver Akt. In summary, we found that lower O2was needed for H2S-dependent hypometabolism in rats compared with previous findings in mice. This highlights the possibility of species differences in physiological responses to H2S. Inhaled H2S exposure also caused tissue injury to the lung and heart, which raises concerns about the therapeutic safety of inhaled H2S. In conclusion, these findings demonstrate the importance of O2in influencing physiological and signaling effects of H2S in mammalian systems.