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 ouabain-sensitive Na,K-ATPases. Previously, we reported that subacute hyperoxia caused an increase in active Na+ transport in rat lungs paralleling Na,K-ATPase upregulation in alveolar Type 2 cells isolated from the same lungs. In the present study we set out to quantify the amiloride-sensitive Na+ flux and ouabain-sensitive active Na+ transport in the isolated-perfused, fluid-filled lung model from rats exposed to 85% O2 for 7 d compared with normoxic control rats. We found increased transpulmonary 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 approximately 62% in control rat lungs and by approximately 87% in lungs from rats exposed to hyperoxia, without further changing permeability for Na+ and mannitol. Ouabain (10(-5)M) perfused through the pulmonary circulation decreased active Na+ transport by approximately 40% in normal rat lungs and by approximately 52% in lungs from rats exposed to hyperoxia. We conclude that active Na+ transport and edema clearance are increased in the subacute hyperoxic lung injury in rats, caused in part by the upregulation of amiloride-sensitive apical Na+ channels and alveolar 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 clearance.
Sznajder
J I
JI
Michael Reese Hospital, University of Illinois at Chicago, USA.
Olivera
W G
WG
Ridge
K M
KM
Rutschman
D H
DH
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D015633:Extravascular Lung Water / Q000378:metabolism*; D018496:Hyperoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011654:Pulmonary Edema / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D015854:Up-Regulation
D000418:Albumins; D008353:Mannitol; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase