ObjectiveEpithelial Na+channels and Na+/K+-adenosine triphosphatase (ATPase) in alveolar epithelium have a very important role in the absorption of excessive fluid from the alveolar space. We examined whether single dexamethasone injection at therapeutic doses would modulate lung epithelial Na+channels and Na+/K+-ATPase and increase alveolar fluid clearance in adult rats.DesignControlled laboratory study.SettingUniversity research laboratory.SubjectsAdult male Sprague-Dawley rats (n = 138).InterventionsRats were intraperitoneally injected with dexamethasone at a dose ranging from 0.02 to 2.0 mg/kg, and allowed free access to food and water.Measurements and Main ResultsAlveolar fluid clearance was determined by measuring the increase in albumin concentration in the lung instillate solution. We discovered a significant increase in alveolar fluid clearance at 48 and 72 hrs after dexamethasone treatment. The effect of dexamethasone was dose dependent. In addition, increased alveolar fluid clearance was associated with a faster recover from hypoxemia, which was induced by filling the alveolar space with instillate solution. The dexamethasone-induced increase in alveolar fluid clearance was inhibited by amiloride and ouabain. Quantitative reverse transcriptase-polymerase chain reaction showed that dexamethasone treatment increased lung &bgr;-epithelial Na+channel mRNA levels. The expression of &ggr;-epithelial Na+channel mRNA was also increased slightly. In contrast, &agr;-epithelial Na+channel mRNA levels did not differ from control levels. There was no change in &agr;1- or &bgr;1-Na+/K+-ATPase mRNA levels over 72 hrs after dexamethasone treatment. However, we found that lung Na+/K+-ATPase hydrolytic activity, determined by monitoring the ouabain-sensitive ATPase hydrolysis, was increased at 48 and 72 hrs after dexamethasone treatment.ConclusionsSingle dexamethasone injection at therapeutic doses is capable of modulating lung epithelial Na+channels and Na+/K+-ATPase and increase alveolar fluid clearance, thereby accelerating recovery from pulmonary edema.