title: Hypoxia downregulates expression and activity of epithelial sodium channels in rat alveolar epithelial cells.
abstract: Decrease in alveolar oxygen tension may induce acute lung injury with pulmonary edema. We investigated whether, in alveolar epithelial cells, expression and activity of epithelial sodium (Na) channels and Na,K-adenosine triphosphatase, the major components of transepithelial Na transport, were regulated by hypoxia. Exposure of cultured rat alveolar cells to 3% and 0% O2 for 18 h reduced Na channel activity estimated by amiloride-sensitive 22Na influx by 32% and 67%, respectively, whereas 5% O2 was without effect. The decrease in Na channel activity induced by 0% O2 was time-dependent, significant at 3 h of exposure and maximal at 12 and 18 h. It was associated with a time-dependent decline in the amount of mRNAs encoding the alpha-, beta-, and gamma-subunits of the rat epithelial Na channel (rENaC) and with a 42% decrease in alpha-rENaC protein synthesis as evaluated by immunoprecipitation after 18 h of exposure. The 0% O2 hypoxia also caused a time-dependent decrease in (1) ouabain-sensitive 86Rubidium influx in intact cells, (2) the maximal velocity of Na,K-ATPase on crude homogenates, and (3) alpha1- and beta1-Na,K-ATPase mRNA levels. Levels of rENaC and alpha1-Na,K-ATPase mRNA returned to control values within 48 h of reoxygenation, and this was associated with complete functional recovery. We conclude that hypoxia induced a downregulation of expression and activity of epithelial Na channels and Na,K-ATPase in alveolar cells. Subsequent decrease in Na reabsorption by alveolar epithelium could participate in the maintenance of hypoxia-induced alveolar edema.
authors.affiliation: Department of Physiology, INSERM U 426, Faculté de Médecine Xavier Bichat, Université Paris 7, France.
authors.forename: C
authors.initials: C
authors.lastname: Planès
authors.forename: B
authors.initials: B
authors.lastname: Escoubet
authors.forename: M
authors.initials: M
authors.lastname: Blot-Chabaud
authors.forename: G
authors.initials: G
authors.lastname: Friedlander
authors.forename: N
authors.initials: N
authors.lastname: Farman
authors.forename: C
authors.initials: C
authors.lastname: Clerici
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D015536:Down-Regulation; D004848:Epithelium / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D015222:Sodium Channels