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

Abstract

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.

The relative balance of GM-CSF and TGF-β1 regulates lung epithelial barrier function

“…Note that chronic alcohol ingestion actually increases the active transport of salt and water across the alveolar epithelium (17,42), which likely counterbalances the increased paracellular permeability in the alcoholic lung. Thus alcohol abuse alone does not cause pulmonary edema but rather renders the lung susceptible to acute edematous injury.…”

NF-κB inhibitors impair lung epithelial tight junctions in the absence of inflammation

“…In otherwise healthy alcoholics, the alveolar barrier is impaired 4,5 although this is compensated by increased fluid clearance. 6,7 Although this in and of itself does not cause ARDS, the alcoholic lung is more sensitive to a second "hit" like ventilator induced lung injury or sepsis, where barrier function is further impaired which overwhelms fluid clearance, leading to increased airspace flooding and subsequent respiratory distress. 8 Although it is well established that inflammation promotes alveolar leak following the second hit, roles for inflammation in alveolar leak in the otherwise healthy alcoholic at baseline are not well characterized.…”

Chronic Alcohol Ingestion Changes the Landscape of the Alveolar Epithelium

“…Basolaterally, Na,K-ATPases facilitate net solute reabsorption, and there are indeed discrepancies in the literature regarding whether chronic alcohol increases Na,K-ATPase activity [6, 23, 45]. Otis et al found that alcohol increased gene expression of α 1, α 2, and β 1 subunits of Na,K-ATPase and protein expression of the α 1 subunit [23].…”

“…Otis et al found that alcohol increased gene expression of α 1, α 2, and β 1 subunits of Na,K-ATPase and protein expression of the α 1 subunit [23]. Dada et al, however, found a time- and dose-dependent decrease in α 1 Na,K-ATPase in the alcoholic lung [6].…”