β-Adrenergic Receptor Stimulation and Adenoviral Overexpression of Superoxide Dismutase Prevent the Hypoxia-mediated Decrease in Na,K-ATPase and Alveolar Fluid Reabsorption

Juan Litvan,Arturo Briva,Mindy S Wilson,G.R Scott Budinger,Jacob Iasha Sznajder,Karen M Ridge

doi:10.1074/jbc.m602064200

Juan Litvan, Arturo Briva + Show 4 more

Open Access

https://doi.org/10.1074/jbc.m602064200

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Abstract

Hypoxia has been shown to cause lung edema and impair lung edema clearance. In the present study, we exposed isolated rat lungs to pO(2) = 40 mm Hg for 60 min or rats to 8% O(2) for up to 24 h and then measured changes in alveolar fluid reabsorption (AFR) and Na,K-ATPase function. Low levels of oxygen severely impaired AFR in both ex vivo and in vivo models. The decrease in AFR was associated with a decrease in Na,K-ATPase activity and protein abundance in the basolateral membranes from peripheral lung tissue of hypoxic rats. Beta-adrenergic agonists restored AFR in rats exposed to 8% O(2) (from 0.02 +/- 0.07 ml/h to 0.59 +/- 0.03 ml/h), which was associated with parallel increases in Na,K-ATPase protein abundance in the basolateral membrane. Hypoxia is associated with increased production of reactive oxygen species. Therefore, we examined whether overexpression of SOD2, manganese superoxide dismutase, would prevent the hypoxia-mediated decrease in AFR. Spontaneously breathing rats were infected with a replication-deficient human type 5 adenovirus containing cDNA for SOD2. An otherwise identical virus that contained no cDNA was used as a control (Adnull). Hypoxic Adnull rats had decreased rates of AFR (0.12 +/- 0.1 ml/h) as compared with hypoxic AdSOD2 and normoxic control rats (0.47 +/- 0.04 ml/h and 0.49 +/- 0.02 ml/h, respectively), with parallel changes in Na,K-ATPase.

Highlights

Hypoxia has been shown to cause lung edema and impair lung edema clearance
The decrease in alveolar fluid reabsorption (AFR) was associated with a decrease in Na,K-ATPase activity and protein abundance in the basolateral membranes from peripheral lung tissue of hypoxic rats. ␤-Adrenergic agonists restored AFR in rats exposed to 8% O2, which was associated with parallel increases in Na,K-ATPase protein abundance in the basolateral membrane
Model—We determined the effect of low levels of oxygen on Effect of Low pO2 on Alveolar Fluid Reabsorption in an in Vivo AFR by perfusing, in different experiments, decreasing levels of Model—We sought to determine whether there was a compenoxygen through the pulmonary circulation of the isolated, per- satory mechanism to prevent the decrease in AFR when anifused rat lung

Summary

Introduction

Hypoxia has been shown to cause lung edema and impair lung edema clearance. In the present study, we exposed isolated rat lungs to pO2 ‫ ؍‬40 mm Hg for 60 min or rats to 8% O2 for up to 24 h and measured changes in alveolar fluid reabsorption (AFR) and Na,K-ATPase function. The decrease in AFR was associated with a decrease in Na,K-ATPase activity and protein abundance in the basolateral membranes from peripheral lung tissue of hypoxic rats. ␤-Adrenergic agonists restored AFR in rats exposed to 8% O2 (from 0.02 ؎ 0.07 ml/h to 0.59 ؎ 0.03 ml/h), which was associated with parallel increases in Na,K-ATPase protein abundance in the basolateral membrane.

Results

Conclusion