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J Physiol Volume 544, Number 2, 537-548, October 15, 2002 DOI: 10.1113/jphysiol.2002.024612
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Journal of Physiology (2002), 544.2, pp. 537-548
© Copyright 2002 The Physiological Society
DOI: 10.1113/jphysiol.2002.024612

Pulmonary oedema fluid induces non-alpha-ENaC-dependent Na+ transport and fluid absorption in the distal lung

Bijan Rafii*, Daniel J. Gillie†, Chris Sulowski*, Vicky Hannam*, Tony Cheung*, Gail Otulakowski*‡, Pierre M. Barker† and Hugh O'Brodovich*‡§

*Lung Biology Programme of the Research Institute of The Hospital for Sick Children, ‡Departments of Paediatrics and §Physiology of the University of Toronto, Toronto, Ontario, Canada M5G 1X8 and †Department of Pediatrics at the University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7220, USA

To determine if pulmonary oedema fluid (EF) alters ion and fluid transport of distal lung epithelium (DLE), EF was collected from rats in acute heart failure. EF, but not plasma, increased amiloride-insensitive short circuit current (Isc) and Na+-K+ ATPase protein content and pump activity of DLE grown in primary culture. Inhibitors of Cl- transport or cGMP-gated cation channels had a significant (P < 0.05), but limited ability to block the increased Isc. EF increased amiloride-insensitive, but not amiloride-sensitive, DLE apical membrane Na+ conductance. The level of mRNA encoding epithelial sodium channel (ENaC) subunits was unchanged (alpha, beta), or decreased (gamma, P < 0.05) in EF-exposed DLE. EF also induced an amiloride-insensitive increase in the potential difference across murine tracheal cysts. Distal lung explants from late gestation wild-type and alpha-ENaC-deficient fetal mice, which normally expand due to liquid secretion, decreased in size due to liquid absorption when exposed to EF. Trypsin digestion or heat treatment of EF abrogated the ability of EF to increase amiloride-insensitive Isc in DLE and liquid absorption by distal lung explants. Thus proteins or protein-dependent factors within cardiogenic EF induce an alpha-ENaC-independent and amiloride-insensitive apical membrane Na+ conductance and liquid absorption in the distal lung.



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