Tohoku J. Exp. Med., 2008, 216(3)

Increased Reabsorption of Alveolar Edema Fluid in the Obese Zucker Rat

GANG MA,¹ XITONG ZHAO,¹ MASAKATSU UENO,¹ MAKOTO TANAKA,¹ YUICHIRO MACHIDA,¹ HIROKAZU AIKAWA,¹ KATSUO USUDA,¹ MOTOYASU SAGAWA,¹ YOSHIMICHI UEDA² and TSUTOMU SAKUMA¹

¹Thoracic Surgery, Kanazawa Medical University, Uchinada, Ishikawa, Japan
²Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan

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 β₂-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 α₁-, β₁-Na, K-ATPase and β₂-adrenoceptor, but not mRNA expression of sodium channel, increased in obese Zucker rats. A selective β₂-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 β₂-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.

keywords —— Obesity; beta-adrenoceptor; terbutaline; lung fluid balance; diabetes.

© 2008 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2008, 216, 223-230

Correspondence: Tsutomu Sakuma, M.D., Thoracic Surgery, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.

e-mail: sakuma-t@kanazawa-med.ac.jp