Ethanol ingestion via glutathione depletion impairs alveolar epithelial barrier function in rats

We determined that rats fed a liquid diet containing ethanol (36% of calori es) for 6 wk had decreased (P < 0.05) net vectorial fluid transport and inc reased (P < 0.05) bidirectional protein permeability across the alveolar ep ithelium in vivo compared with rats fed a control diet. However, both group s increased (P, 0.05) fluid transport in response to epinephrine (10(-5) M) stimulation, indicating that transcellular sodium transport was intact. In parallel, type II cells isolated from ethanol-fed rats and cultured for 8 days formed a more permeable monolayer as reflected by increased (P< 0.05) leak of [C-14] inulin. However, type II cells from ethanol-fed rats had mor e sodium-permeant channels in their apical membranes than type II cells iso lated from control-fed rats, consistent with the preserved response to epin ephrine in vivo. Finally, the alveolar epithelium of ethanol-fed rats suppl emented with L-2-oxothiaxolidine-4-carboxylate (Procysteine), a glutathione precursor, had the same (P< 0.05) net vectorial fluid transport and bidire ctional protein permeability in vivo and permeability to [C-14] inulin in v itro as control-fed rats. We conclude that chronic ethanol ingestion via gl utathione deficiency increases alveolar epithelial intercellular permeabili ty and, despite preserved or even enhanced transcellular sodium transport, renders the alveolar epithelium susceptible to acute edematous injury.