Pulmonary oedema fluid induces non-alpha-ENaC-dependent Na(+) transport and fluid absorption in the distal lung.
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 (I(sc)) 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 I(sc). 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 I(sc) 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.
Rafii
Bijan
B
Lung Biology Programme of the Research Institute of The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
Gillie
Daniel J
DJ
Sulowski
Chris
C
Hannam
Vicky
V
Cheung
Tony
T
Otulakowski
Gail
G
Barker
Pierre M
PM
O'Brodovich
Hugh
H
D000042:Absorption; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport; D001826:Body Fluids / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D053503:Epithelial Sodium Channels; D004848:Epithelium / Q000503:physiopathology; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D011654:Pulmonary Edema / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000975:Antioxidants; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D015222:Sodium Channels; D000584:Amiloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase