Na, K-ATPase overexpression improves alveolar fluid clearance in a rat model of elevated left atrial pressure

Acute elevation of left atrial pressure (LAP) increases extravascular water and impairs active Na(+) transport in rat lungs. We have reported that overexpression of Na,K-ATPase subunit genes in the alveolar epithelium increases alveolar fluid clearance (AFC) in normal and injured rat lungs with norm...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2002-01, Vol.105 (4), p.497-501
Main Authors: AZZAM, Zaher S, DUMASIUS, Vidas, SALDIAS, Fernando J, ADIR, Yochai, SZNAJDER, Jacob I, FACTOR, Phillip
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Animals
Biological and medical sciences
Blood Pressure
Cardiology. Vascular system
Cell Membrane Permeability
Gene Transfer Techniques
Genetic Vectors
Heart
Heart Atria - physiopathology
Heart failure, cardiogenic pulmonary edema, cardiac enlargement
In Vitro Techniques
Ion Transport
Male
Medical sciences
Pulmonary Alveoli - metabolism
Pulmonary Edema - metabolism
Pulmonary Edema - physiopathology
Rats
Rats, Sprague-Dawley
Sodium - metabolism
Sodium-Potassium-Exchanging ATPase - genetics
Sodium-Potassium-Exchanging ATPase - metabolism
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Summary:Acute elevation of left atrial pressure (LAP) increases extravascular water and impairs active Na(+) transport in rat lungs. We have reported that overexpression of Na,K-ATPase subunit genes in the alveolar epithelium increases alveolar fluid clearance (AFC) in normal and injured rat lungs with normal LAP. We reasoned that adenovirus-mediated transfer of an Na,K-ATPase beta-subunit gene to the alveolar epithelium could improve AFC in rat lungs in the presence of acutely elevated LAP. Normal rats were infected with 4x10(9) plaque-forming units of E1a(-)/E3(-) recombinant adenoviruses that contained a cytomegalovirus promoter coupled to a rat Na,K-ATPase beta(1)-subunit cDNA (adbeta(1)) or no cDNA (adNull) 7 days before study. Na,K-ATPase alpha(1)- and beta(1)-subunit abundance in basolateral cell membranes isolated from the peripheral lung was significantly increased in adbeta(1)-infected lungs compared with sham and adNull-infected controls. In all groups, elevation of LAP reduced membrane-bound Na,K-ATPase abundance; however, abundance in adbeta(1)-infected lungs remained greater than in controls. AFC, measured with a fluid-filled isolated lung preparation in the presence of elevated LAP (15 cmH(2)O), in Na,K-ATPase beta(1)-subunit-overexpressing lungs was up to 100% greater than in controls and was not different from rats studied at normal LAP (0 cmH(2)O). These data suggest that alveolar overexpression of an Na,K-ATPase beta(1)-subunit can counteract downregulation of membrane-bound solute transporters owing to elevated pulmonary vascular pressures and can restore active Na(+) transport and AFC in this rat model of acute hydrostatic pulmonary edema.
ISSN:0009-7322
1524-4539
DOI:10.1161/hc0402.102848