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Author Notes:

Reprint requests: Jeffrey S. Otis, PhD, Atlanta VAMC (151-P) 1670 Clairmont Road, Decatur, GA 30033; Fax: (404) 728-7750; jsotis@emory.edu

JO and PM have co-first author status.


Research Funding:

Supported by NIAAA (T32 AA013528, F32 AA016262, P50 AA013757) and the Department of Veterans Affairs (Merit Review).


  • Alcohol
  • Acute Respiratory Distress Syndrome
  • Edema
  • Lung

Na,K-ATPase Expression Is Increased in the Lungs of Alcohol-Fed Rats


Journal Title:

Alcoholism: Clinical and Experimental Research


Volume 32, Number 4


, Pages 699-705

Type of Work:

Article | Post-print: After Peer Review


Background Alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome (ARDS), a disease characterized by diffuse alveolar epithelial damage, lung edema, and consequent severe hypoxemia. Chronic alcohol abuse increases alveolar epithelial permeability both in vitro and in vivo, in part due to altered tight junction formation. However, both alcohol-fed animals and otherwise healthy alcoholic humans do not have pulmonary edema at baseline, even though their lungs are highly susceptible to acute edematous injury in response to inflammatory stresses. This suggests that active fluid transport by the alveolar epithelium is preserved or even augmented in the alcoholic lung. Chronic alcohol ingestion increases expression of apical sodium channels in the alveolar epithelium; however, its effects on the Na,K-ATPase complex that drives sodium and fluid transport out of the alveolar space have not been examined. Methods Age- and gender-matched Sprague–Dawley rats were fed the Lieber–DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 6 weeks. Gene and protein expression of lung Na,K-ATPase α1, α2, and β1 subunits were quantified via real-time PCR and immunobiological analyses, respectively. Alcohol-induced, Na,K-ATPase-dependent epithelial barrier dysfunction was determined by calculating lung tissue wet:dry ratios following an ex vivo buffer-perfused challenge for 2 hours in the presence of ouabain (10−4 M), a Na, K-ATPase inhibitor. Results Chronic alcohol ingestion significantly increased gene and protein expression of each Na,K-ATPase subunit in rat lungs. Immunohistochemical analyses of the alcoholic lung also revealed that protein expression of the Na,K-ATPase α1 subunit was increased throughout the alveolar epithelium. Additionally, lungs isolated from alcohol-fed rats developed more edema than comparably treated lungs from control-fed rats, as reflected by increased lung tissue wet:dry ratios. Conclusions These findings indicate that chronic alcohol ingestion, which is known to increase alveolar epithelial paracellular permeability, actually increases the expression of Na,K-ATPase in the lung as a compensatory mechanism. This provides a potential explanation as to why the otherwise healthy alcoholic does not have evidence of pulmonary edema at baseline.

Copyright information:

© 2008 by the Research Society on Alcoholism.

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