Mechanisms of lung liquid clearance during hyperoxia in isolated rat lungs

Am J Respir Crit Care Med. 1995 May;151(5):1519-25. doi: 10.1164/ajrccm.151.5.7735609.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / metabolism
  • Animals
  • Biological Transport
  • Extravascular Lung Water / metabolism*
  • Hyperoxia / metabolism*
  • In Vitro Techniques
  • Lung / metabolism*
  • Male
  • Mannitol / metabolism
  • Ouabain / pharmacology
  • Pulmonary Edema / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sodium / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Up-Regulation


  • Albumins
  • Mannitol
  • Ouabain
  • Sodium
  • Sodium-Potassium-Exchanging ATPase