Metabolic and cardiac signaling effects of inhaled hydrogen sulfide and low oxygen in male rats.
Metabolic and cardiac signaling effects of inhaled hydrogen sulfide and low oxygen in male rats.
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DOI：
10.1152/japplphysiol.01598.2011
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发表时间：
2012-05
影响因子：
3.3
通讯作者：
A. Stein;Zhengkuan Mao;J. Morrison;M. Fanucchi;E. Postlethwait;R. Patel;D. Kraus;J. Doeller;S. Bailey
中科院分区：
文献类型：
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作者：
A. Stein;Zhengkuan Mao;J. Morrison;M. Fanucchi;E. Postlethwait;R. Patel;D. Kraus;J. Doeller;S. Bailey
吸入低浓度硫化氢（H（2）S）可导致小鼠代谢降低。在离体系统中，H（2）S的生物效应通过降低O（2）张力而增强。基于此，我们假设O（2）张力降低会增加体内H（2）S介导的低代谢。为了测试这一点，雄性Sprague-Dawley大鼠暴露于80 ppm H（2）S，21% O（2）或10.5% O（2）6小时，然后在室内空气中恢复1小时。暴露于含10.5%O（2）的硫化氢中的大鼠体温和呼吸与暴露前水平相比显著降低。在两种O（2）水平下给予H（2）S可降低心率，恢复1小时后心率未恢复至暴露前水平。吸入硫化氢可引起肺上皮脱落和血浆肌酸激酶MB活性增加。在心脏和肝脏中也测量了吸入H（2）S对促存活信号传导的影响。21%O（2）中的H（2）S增加心脏中的Akt-P（Ser 473）和GSK-3β-P（Ser 9），而10.5%O（2）中的H（2）S降低磷酸化，表明O（2）依赖于调节心脏信号通路。吸入硫化氢和低氧对肝脏Akt无影响。总之，我们发现，与先前在小鼠中的发现相比，大鼠中H（2）S依赖性代谢减退需要较低的O（2）。这凸显了物种对H（2）S的生理反应存在差异的可能性。吸入H2S也会对肺和心脏造成组织损伤，这引起了人们对吸入H2S治疗安全性的担忧。总之，这些发现表明O（2）在影响H（2）S在哺乳动物系统中的生理和信号作用方面的重要性。
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.