Hyperoxic effects on alveolar sodium resorption and lung Na-K-ATPase

Active Na⁺ transport by the alveolar epithelium keeps alveoli relatively dry. Hyperoxia increases epithelial permeability, resulting in pulmonary edema. We sought to determine whether active Na⁺ resorption from the air spaces and Na-K-ATPase activity increased in rats exposed to >95% O₂ for 60 h. The permeability x surface area products for unidirectional resorption of alveolar [¹⁴C]sucrose (PS(sucrose)) and ²²Na⁺ (PS(Na⁺)) were measured in isolated, perfused rat lungs immediately after hyperoxia and after 3 and 7 days of recovery in room air. At 60 h of hyperoxia, the mean PS(sucrose) and PS(Na⁺) increased from 6.71 ± 0.8 x 10^-5 to 12.6 ± 1.6 x 10^-5 cm³/s (P = 0.029) and from 23.6 ± 1.1 x 10^-5 to 31.0 ± 1.6 x 10^{- 5} cm³/s (P < 0.008), respectively. However, the values in individual rats ranged widely from no change to nearly a fourfold increase. Subgroup analysis revealed that benzamil- or amiloride-sensitive (transcellular) PS(Na⁺) was significantly reduced in the exposed lungs with normal PS(sucrose) but was maintained in the lungs with high PS(sucrose). By day 3 of recovery, mean Na⁺ and sucrose fluxes returned to values similar to control. Na-K-ATPase membrane hydrolytic maximal velocity (V(max)) activity fell significantly immediately after hyperoxic exposure but recovered to normal values by day 3 of recovery. The Na-K-ATPase β₁-subunit antigenic signal did not significantly change, whereas the α₁-subunit levels increased during recovery. In summary, there was a heterogeneous response of different rats to acute hyperoxia. Hyperoxia led to complex, nonparallel changes in Na⁺ pump antigenic protein, hydrolytic activity, and unidirectional active Na⁺ resorption. Active Na⁺ transport was differentially affected, depending on degree of injury, but permeability and transport normalized by day 3 of recovery.