Hypoxia reversibly inhibits epithelial sodium transport but does not inhibit lung ENaC or Na-K-ATPase expression.
Hypoxia reduces alveolar liquid clearance and the nasal potential difference, a marker of airway epithelial sodium transport. The mechanisms underlying this impaired epithelial sodium transport in vivo remain uncertain. We hypothesized that epithelial sodium transport impaired by hypoxia would recover quickly with reoxygenation and that hypoxia decreases the expression of lung epithelial sodium channels and Na,K-ATPases. We studied adult rats exposed to normoxia, hypoxia (Fi(O(2)) = 0.1) for 24 h, or hypoxia followed by recovery in normoxia. Nasal potential differences decreased by 40% with hypoxia (P < 0.001), returning to baseline levels with reoxygenation. Lung Na,K-ATPase activity decreased by 40% with hypoxia (P = 0.003), recovering to baseline levels with reoxygenation. Lung expression of mRNA encoding for epithelial sodium channel (ENaC)-alpha, -beta, and -gamma or for Na,K-ATPase-alpha(1) did not change significantly with hypoxia or recovery nor did lung expression of ENaC-alpha, ENaC-beta, Na,K-ATPase-alpha(1), or Na,K-ATPase-beta(1) protein. We conclude that subacute exposure to moderate hypoxia reversibly impairs airway epithelial sodium transport and lung Na,K-ATPase activity but that those changes are not due to changes in the lung expression of sodium-transporting proteins.
Carpenter
Todd C
TC
Department of Pediatrics and Cardiovascular-Pulmonary Research Laboratory, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA. todd.carpenter@uchsc.edu
Schomberg
Stacey
S
Nichols
Christopher
C
Stenmark
Kurt R
KR
Weil
John V
JV
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D004594:Electrophysiology; D053503:Epithelial Sodium Channels; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D008168:Lung / Q000378:metabolism*; D008297:Male; D009297:Nasal Mucosa / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D002352:Carrier Proteins; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; C507050:Scnn1b protein, rat; D015222:Sodium Channels; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase