Single dexamethasone injection increases alveolar fluid clearance in adult rats*

Abstract

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. Controlled laboratory study. University research laboratory. Adult male Sprague-Dawley rats (n = 138). 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. 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 beta-epithelial Na+ channel mRNA levels. The expression of gamma-epithelial Na+ channel mRNA was also increased slightly. In contrast, alpha-epithelial Na+ channel mRNA levels did not differ from control levels. There was no change in alpha1- or beta1-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. 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.