IMPAIRMENT OF CATION-TRANSPORT IN A549 CELLS AND RAT ALVEOLAR EPITHELIAL-CELLS BY HYPOXIA

A reduced cation reabsorption across the alveolar epithelium decreases water reabsorption from the alveoli and could diminish clearing accum ulated fluid. To test whether hypoxia restricts cation transport in al veolar epithelial cells, cation uptake was measured in rat lung alveol ar type II pneumocytes (AII cells) in primary culture and in A549 cell s exposed to normoxia and hypoxia. In AII and A549 cells, hypoxia caus ed a Po-2-dependent inhibition of the Na-K pump, of Na-K-2Cl cotranspo rt, and of total and amiloride-sensitive Na-22 uptake. Nifedipine fail ed to prevent hypoxia-induced transport inhibition in both cell types. In A549 cells, the inhibition of the Na-K pump and Na-K-2Cl cotranspo rt occurred within similar to 30 min of hypoxia, was stable >20 h, and was reversed by 2 h of reoxygenation. There was also a reduction in c ell membrane-associated Na-K-ATPase and a decrease in Na-K-2Cl cotrans port flux after full activation with calyculin A, indicating a decreas ed transport capacity. [C-14]serine incorporation into cell proteins w as reduced in hypoxic A549 cells, but inhibition of protein synthesis with cycloheximide did not reduce ion transport. In AII and A549 cells , ATP levels decreased slightly, and ADP and the ATP-to-ADP ratio were unchanged after 4 h of hypoxia. In A549 cells, lactate, intracellular Na, and intracellular K were unchanged. These results indicate that h ypoxia inhibits apical Na entry pathways and the basolateral Na-K pump in A549 cells and rat AII pneumocytes in culture, indicating a hypoxi a-induced reduction of transepithelial Na transport and water reabsorp tion by alveolar epithelium. If similar changes occur in vivo, the imp aired cation transport across alveolar epithelial cells might contribu te to the formation of hypoxic pulmonary edema.