Epithelial Sodium Channel Was Involved In H₂S Induced Acute Pulmonary Edema And The Mechanism Of Dexamethasone On Protection

Acute pulmonary edema is one of the major outcomes from exposure to high levels of hydrogen sulfide(H2S).However,the mechanisms are largely unknown.The present work was focused on the effects of epithelial sodium channel(ENaC)on H2S induced acute pulmonary edema and the mechanism of dexamethasone on protection.The SD rats were exposed to the sublethal concentrantions of inhaled H2S,and the pulmonary histological changes were evaluated by Hematoxyline-eosin staining.Moreover,the electron microscope assay was performed to evaluate,the damage of lung epithelial cells as well.The whole cell patch clamp data showed that H2S significantly inhibited ENaC currents in human lung cell line A549.In parallel,the alveolar fluid clearence(AFC)was markedly decreased after 6h exposure to H2S in SD rat.Therefore,the expression of ENaC was detected.Our results revealed that ENaC was obviously decreased both in mRNA and protein level after H2S treatment,and the effects were associated with the ERK1/2 pathway,since ERK1/2 was obviously activated after H2S exposure and inhibited the ERK1/2 pathway by PD98059 significantly decreased ENaC expression.Our results suggested that ENaC was involved in H2S induced acute pulmonary edema.Next,pre-treated with dexamethasone obviously retarded the above-mentioned process.Furthermore,dexamethasone obviously prevented H2S-mediated ERK1/2 activation.These results suggested that dexamethasone played protective roles in H2S-induced pulmonary edema and ENaC may become a potential therapeutic target for pulmonary edema induced by H2S.