MECHANISMS OF LUNG LIQUID CLEARANCE DURING HYPEROXIA IN ISOLATED RAT LUNGS

Sodium transport across the lung epithelium is predominantly effected by apical amiloride-sensitive Na+ channels and basolaterally located o uabain-sensitive Na,K-ATPases. Previously we reported that subacute hy peroxia causes an increase in active Na+ transport in rat lungs parall eling Na,K-ATPase upregulation in alveolar Type 2 cells isolated from the same lungs. In the present study we set out to quantify the amilor ide-sensitive Na+ flux and ouabain-sensitive active Na+ transport in t he isolated-perfused, fluid-filled lung model from rats exposed to 85% O-2 for 7 d compared with normoxic control rats. We found increased t ranspulmonary albumin flux and permeability to small solutes (Na+ and mannitol) in hyperoxic rat lungs compared with controls. Amiloride (10 (-5) M) instilled into rat airspaces inhibited active Na+ transport by similar to 62% in control rat lungs and by similar to 87% in lungs fr om rats exposed to hyperoxia, without further changing permeability fo r Na+ and mannitol. Ouabain (10(-5) M) perfused through the pulmonary circulation decreased active Na+ transport by similar to 40% in normal rat lungs and by similar to 52% in lungs from rats exposed to hyperox ia. We conclude that active Na+ transport and edema clearance are incr eased in the subacute hyperoxic lung injury in rats, caused in part by the upregulation of amiloride-sensitive apical Na+ channels and alveo lar epithelial Na,K-ATPases. Conceivably, the upregulation of alveolar epithelial Na+ channels and Na,K-ATPases protects against the effects of lung injury in this model by contributing to effective edema clear ance.