title: Epithelial sodium channel is involved in H2S-induced acute pulmonary edema.
abstract: Acute pulmonary edema is one of the major outcomes of exposure to high levels of hydrogen sulfide (H2S). However, the mechanisms involved in H2S-induced acute pulmonary edema are still poorly understood. Therefore, the present study is designed to evaluate the role of epithelial sodium channel (ENaC) in H2S-induced acute pulmonary edema. The Sprague-Dawley rats were exposed to sublethal concentrations of inhaled H2S, then the pulmonary histological and lung epithelial cell injury were evaluated by hematoxylin-eosin staining and electron microscopy, respectively. In addition to morphological investigation, our results also revealed that H2S exposure significantly decreased the alveolar fluid clearance and increased the lung tissue wet-dry ratio. These changes were demonstrated to be associated with decreased ENaC expression. Furthermore, the extracellular-regulated protein kinases 1/2 pathway was demonstrated to be implicated in H2S-mediated ENaC expression, because PD98059, an ERK1/2 antagonist, significantly mitigated H2S-mediated ENaC down-regulation. Therefore, our results show that ENaC might represent a novel pharmacological target for the treatment of acute pulmonary edema induced by H2S and other hazardous gases.
authors.affiliation: a Department of Emergency Medicine , The First Affiliated Hospital of Nanjing Medical University , Nanjing , Jiangsu , P.R. China .
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: b Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health , Nanjing Medical University , Nanjing , Jiangsu , P.R. China , and.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a Department of Emergency Medicine , The First Affiliated Hospital of Nanjing Medical University , Nanjing , Jiangsu , P.R. China .
authors.forename: Chenglei
authors.initials: C
authors.lastname: Su
authors.affiliation: a Department of Emergency Medicine , The First Affiliated Hospital of Nanjing Medical University , Nanjing , Jiangsu , P.R. China .
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: a Department of Emergency Medicine , The First Affiliated Hospital of Nanjing Medical University , Nanjing , Jiangsu , P.R. China .
authors.forename: Huazhong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: c Department of Occupational Disease Prophylactic-Therapeutic Institution , Jiangsu Provincial Center for Disease Prevention and Control , Nanjing , Jiangsu , P.R. China.
authors.forename: Baoli
authors.initials: B
authors.lastname: Zhu
authors.affiliation: c Department of Occupational Disease Prophylactic-Therapeutic Institution , Jiangsu Provincial Center for Disease Prevention and Control , Nanjing , Jiangsu , P.R. China.
authors.forename: Hengdong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: b Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health , Nanjing Medical University , Nanjing , Jiangsu , P.R. China , and.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
authors.affiliation: b Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health , Nanjing Medical University , Nanjing , Jiangsu , P.R. China , and.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Department of Emergency Medicine , The First Affiliated Hospital of Nanjing Medical University , Nanjing , Jiangsu , P.R. China .
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000633:toxicity*; D019570:Inhalation Exposure / Q000009:adverse effects; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053503:Epithelial Sodium Channels; D006862:Hydrogen Sulfide
keywords: Acute pulmonary edema; ERK1/2; alveolar fluid clearance; epithelial sodium channel; hydrogen sulfide