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(Circulation. 2002;105:497.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Na,K-ATPase Overexpression Improves Alveolar Fluid Clearance in a Rat Model of Elevated Left Atrial Pressure

Zaher S. Azzam, MD; Vidas Dumasius, BS; Fernando J. Saldias, MD; Yochai Adir, MD; Jacob I. Sznajder, MD; Phillip Factor, DO

From Technion (Z.S.A., Y.A.), Israel Institute of Technology, Haifa, Israel; Evanston Northwestern Healthcare (V.D., P.F.), Evanston, Ill; Division of Pulmonary and Critical Care Medicine (Y.A., J.I.S., P.F.), Northwestern University, Chicago, Ill; and Universidad Católica de Chile (F.J.S.), Santiago, Chile.

Correspondence to Phillip Factor, DO, Pulmonary and Critical Care Medicine, Evanston Northwestern Healthcare, 2650 Ridge Rd, Evanston, IL 60201. E-mail pfactor{at}northwestern.edu

Background— 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 ß-subunit gene to the alveolar epithelium could improve AFC in rat lungs in the presence of acutely elevated LAP.

Methods and Results— Normal rats were infected with 4x10⁹ plaque-forming units of E1a^-/E3^- recombinant adenoviruses that contained a cytomegalovirus promoter coupled to a rat Na,K-ATPase ß₁-subunit cDNA (adß₁) or no cDNA (adNull) 7 days before study. Na,K-ATPase ₁- and ß₁-subunit abundance in basolateral cell membranes isolated from the peripheral lung was significantly increased in adß₁-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 adß₁-infected lungs remained greater than in controls. AFC, measured with a fluid-filled isolated lung preparation in the presence of elevated LAP (15 cmH₂O), in Na,K-ATPase ß₁-subunit-overexpressing lungs was up to 100% greater than in controls and was not different from rats studied at normal LAP (0 cmH₂O).

Conclusions— These data suggest that alveolar overexpression of an Na,K-ATPase ß₁-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.

Key Words: epithelium • genes • viruses • heart failure • edema

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