Single dexamethasone injection increases alveolar fluid clearance in adult rats^*

Abstract

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.