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.

• Acute pulmonary edema
• alveolar fluid clearance
• epithelial sodium channel
• ERK1/2
• hydrogen sulfide

Declaration of interest

This work was supported by the Medical Innovation Team Foundation of Jiangsu Province (LJ201122), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and the Science and Technology Plan Project of Jiangsu Province (SBL2014020070). This publication is solely the responsibility of the authors, and there is no conflict of interest, including financial conflicts.