Active sodium transport and alveolar epithelial Na-K-ATPase increase during subacute hyperoxia in rats

Abstract

Active Na+ transport and lung edema clearance were studied in a model of lung injury caused by sublethal oxygen exposure. Rats exposed to 85% O2 for 7 days were studied at 0, 7, 14, and 30 days after removal from the hyperoxic chamber and compared with room air controls. In the isolated-perfused, fluid-filled rat lung, albumin flux from the perfusate into the air spaces increased after oxygen exposure and returned to control values after 7 days of recovery. However, permeability to small solutes (Na+ and mannitol) normalized only after 30 days of recovery from hyperoxia. Active Na+ transport increased immediately after oxygen exposure and returned to control values 7 days after removal from hyperoxic chamber. Na-K-adenosinetriphosphatase (ATPase) activity, and protein expression in alveolar epithelial type II cells obtained at the end of the isolated lung experiments increased significantly after the oxygen exposure compared with controls in association with the increased active Na+ transport. We conclude that active Na+ transport and lung liquid clearance are increased in the subacute hyperoxic phase of lung injury in rats, due in part to the upregulation of alveolar epithelial Na-K-ATPases. Conceivably, this behavior protects against the effects of lung injury by allowing the injured lung to clear edema more effectively. Accordingly, this upregulation may be targeted as a strategy to diminish edema in patients with lung injury.

Hyperbaric oxygenation upregulates rat lung Na,K-ATPase

“…We have previously reported that rats exposed to 85% oxygen for 7 days had increased Na,K-ATPase number and function in AT2 cells, as compared to controls, and this was associated with an increase in active Na + transport in the isolated rat lung model [6,17]. Possibly, in these two models, reactive oxygen species at the alveolar surface initiate a cascade of events that includes increased cytoplasmic calcium [20], cyclic adenosine monophosphate (cAMP), S6 kinases, etc.…”

“…We have previously observed that rats exposed to 85% oxygen for 7 days exhibited increased active Na + transport across the lung epithelium, as well as increased Na,Kadenosine triphosphate (ATPase) protein function in the alveolar epithelium [6]. Our previous study in the normobaric hyperoxia model and others [7], suggest that upregulation of the Na,K-ATPase in rat lungs are part of the protective mechanism against alveolar flooding.…”

“…Pretreatment with interleukin-1 (IL-1), endotoxin, or 85% oxygen exposure for 7 days, however, has been shown to confer protection and improve survival to subsequent 100% oxygen exposure [14][15][16]. Lung tolerance to hyperoxia is probably the result of upregulation of antioxidants and other protective mechanisms, such as increased clearance of oedema fluid via, among other mechanisms, enhanced lung Na,K-ATPase activity [6,7,17]. Other modalities, such as pretreatment with oxygen radical scavengers or delivery of antioxidants complexed to liposomes into the airways have also been shown to be protective against hyperoxia [18].…”

Functional ion channels in pulmonary alveolar type I cells support a role for type I cells in lung ion transport

“…Electroneutrality is conserved with Cl Ϫ movement via CFTR in both TI and TII cells, and͞or paracellularly through tight junctions or possibly via an as yet unidentified apical Cl Ϫ -HCO 3 Ϫ exchanger. Because most eukaryotic cells extrude H ϩ to regulate intracellular pH (35), the net effect of uptake via a Cl Ϫ -HCO 3 Ϫ exchange would be to absorb Cl Ϫ and extrude HCO 3 Ϫ , which, when combined with H ϩ in the alveolar lumen, would produce CO 2 , which is exhaled. Extensive experiments characterizing the various channels and the mechanisms by which they are regulated will be necessary to understand the pathways by which anions are transported in the alveolus.…”

“…Alveolar flooding resulting from cardiogenic pulmonary edema or acute lung injury impairs gas diffusion across the air͞blood barrier; an increase in alveolar fluid clearance restores a normal air͞blood barrier. Alveolar fluid transport from alveolar to interstitial spaces, driven by active Na ϩ transport across the alveolar epithelium (2), can be inhibited either by the addition of amiloride, a Na ϩ channel inhibitor, to the alveolar space, or ouabain, a Na ϩ ,K ϩ -ATPase inhibitor, to the vascular bed (3), suggesting that the alveolar epithelium is the major site of Na ϩ transport and fluid absorption in the adult lung.…”