Na,K-ATPase overexpression improves alveolar fluid clearance in a rat model of elevated left atrial pressure.
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 beta-subunit gene to the alveolar epithelium could improve AFC in rat lungs in the presence of acutely elevated LAP.


RESULTS
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).


CONCLUSIONS
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.
Azzam
Zaher S
ZS
Technion, Israel Institute of Technology, Haifa, Israel.
Dumasius
Vidas
V
Saldias
Fernando J
FJ
Adir
Yochai
Y
Sznajder
Jacob I
JI
Factor
Phillip
P
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001794:Blood Pressure; D002463:Cell Membrane Permeability; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006325:Heart Atria / Q000503:physiopathology; D066298:In Vitro Techniques; D017136:Ion Transport; D008297:Male; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011654:Pulmonary Edema / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism
D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase