Alveolar Fluid Clearance in Zucker Rats

Diabetic patients have a decreased incidence of acute respiratory distress syndrome, but the mechanism responsible for the decreased incidence is uncertain. Reabsorption of alveolar edema fluid (alveolar fluid clearance) has been considered to play an important role in resolution of acute respiratory distress syndrome. However, little is known regarding alveolar fluid clearance in diabetes mellitus. Since the obese Zucker rat has been used as an experimental model for diabetes mellitus, we determined if alveolar fluid clearance increased in the obese Zucker rat. First, we compared alveolar fluid clearance in obese Zucker rats with that in lean Zucker rats and Sprague-Dawley (SD) rats. Then, we determined the role of sodium channel, Na,K-ATPase, and β 2-adrenoceptor, which drives alveolar fluid clearance, in obese Zucker rats. Alveolar fluid clearance was estimated by the progressive increase in alveolar albumin concentrations in the isolated lungs. We found that basal alveolar fluid clearance in obese Zucker rats was two-fold greater than that in lean Zucker rats and SD rats. The mRNA expression of α 1-, β 1-Na, K-ATPase and β 2adrenoceptor, but not mRNA expression of sodium channel, increased in obese Zucker rats. A selective β 2-agrenergic antagonist, but not a Na, K-ATPase inhibitor, specifically inhibited the increase in alveolar fluid clearance in obese Zucker rats. These results indicate that overexpression of β 2-adrenoceptor primarily increases basal alveolar fluid clearance in the obese Zucker rat. We speculate that the stimulation of alveolar fluid clearance ameliorates acute respiratory distress syndrome in patients with diabetes mellitus. ──── Obesity; beta-adrenoceptor; terbutaline; lung fluid balance; diabetes. Tohoku J. Exp. Med., 2008, 216 (3), 223-230. © 2008 Tohoku University Medical Press