Chronic ethanol ingestion increases epithelial sodium channel activity in C57BL/6 lung

Abstract

It is clear that a critical component of salt and water transport by the lungs depends on precise control of epithelial sodium channel (ENaC) activity, which generates the osmotic driving force for net transport of solute out of the air space. Chronic ethanol (EtOH) ingestion alters the signal transduction pathway leading to normal ENaC activity. We show that chronic EtOH ingestion in 12 week old C57BL/6 mice increases expression of ENaC, NADPH oxidase (Nox) 2, and Nox 4 protein (1.7, 1.5, and 2.8 fold, respectively) using western blot analysis. Real time PCR analysis of Rac‐guanine nucleotide exchange factors (which mediate activation of Nox) reveals that Arhgef7, Sos1, Sos2, Tiam1, and Ras‐GRF2 transcripts are significantly down‐regulated in EtOH lung compared to normal healthy lung. In vivo radiographic imaging indicates that these changes in cellular signaling lead to an enhanced rate of lung fluid clearance in EtOH animals following a tracheal saline challenge of 5uL/g body weight. We conclude that chronic ethanol ingestion activates NADPH oxidase, which oxidizes the alveolar environment in order to stimulate redox sensitive ENaC activity. This research was supported by SIRE awarded to DT, and R00‐HL‐09222601.