Beta-adrenergic receptor stimulation and adenoviral overexpression of superoxide dismutase prevent the hypoxia-mediated decrease in Na,K-ATPase and alveolar fluid reabsorption.

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.

• Authors: Juan Litvan, Arturo Briva, Mindy S Wilson, G R Scott Budinger, Jacob Iasha Sznajder, Karen M Ridge
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 281 Issue 29 Pg. 19892-8 (Jul 21 2006) ISSN: 0021-9258 [Print] United States
• PMID: 16636055 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Receptors, Adrenergic, beta
• Superoxide Dismutase
• Sodium-Potassium-Exchanging ATPase
• Oxygen

Topics

• Adenoviridae (genetics)
• Animals
• Bronchoalveolar Lavage Fluid (virology)
• Cell Hypoxia (physiology)
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Viral
• Oxygen
• Partial Pressure
• Pulmonary Alveoli (physiology)
• Pulmonary Edema (prevention & control)
• Rats
• Receptors, Adrenergic, beta (physiology)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Superoxide Dismutase (genetics)