Single dexamethasone injection increases alveolar fluid clearance in adult rats

Objective: Epithelial 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. Design: Controlled laboratory study. Setting: University research laboratory. Subjects: Adult male Sprague-Dawley rats (n = 138). Interventions: Rats 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 Results: Alveolar 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 β-epithelial Na⁺ channel mRNA levels. The expression of γ-epithelial Na⁺ channel mRNA was also increased slightly. In contrast, α-epithelial Na⁺ channel mRNA levels did not differ from control levels. There was no change in α1- or β1-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. Conclusions: Single 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.