Defective respiratory amiloride-sensitive sodium transport predisposes to pulmonary oedema and delays its resolution in mice

Détails

ID Serval
serval:BIB_962AB01443C3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Defective respiratory amiloride-sensitive sodium transport predisposes to pulmonary oedema and delays its resolution in mice
Périodique
Journal of Physiology
Auteur(s)
Egli M., Duplain H., Lepori M., Cook S., Nicod P., Hummler E., Sartori C., Scherrer U.
ISSN
0022-3751 (Print)
Statut éditorial
Publié
Date de publication
11/2004
Peer-reviewed
Oui
Volume
560
Numéro
Pt 3
Pages
857-65
Notes
Comparative Study Journal Article Research Support, Non-U.S. Gov't --- Old month value: Nov 1
Résumé
Pulmonary oedema results from an imbalance between the forces driving fluid into the airspace and the biological mechanisms for its removal. In mice lacking the alpha-subunit of the amiloride-sensitive sodium channel (alphaENaC(-/-)), impaired sodium transport-mediated lung liquid clearance at birth results in neonatal death. Transgenic expression of alphaENaC driven by a cytomegalovirus (CMV) promoter (alphaENaC(-/-)Tg+) rescues the lethal pulmonary phenotype, but only partially restores respiratory sodium transport in vitro. To test whether this may also be true in vivo, and to assess the functional consequences of this defect on experimental pulmonary oedema, we measured respiratory transepithelial potential difference (PD) and alveolar fluid clearance (AFC), and quantified pulmonary oedema during experimental acute lung injury in these mice. Both respiratory PD and AFC were roughly 50% lower (P < 0.01) in alphaENaC(-/-)Tg+ than in control mice. This impairment was associated with a significantly larger increase of the wet/dry lung weight ratio in alphaENaC(-/-)Tg+ than in control mice, both after exposure to hyperoxia and thiourea. Moreover, the rate of resolution of thiourea-induced pulmonary oedema was more than three times slower (P < 0.001) in alphaENaC(-/-)Tg+ mice. alphaENaC(-/-)Tg+ mice represent the first model of a constitutively impaired respiratory transepithelial sodium transport, and provide direct evidence that this impairment facilitates pulmonary oedema in conscious freely moving animals. These data in mice strengthen indirect evidence provided by clinical studies, suggesting that defective respiratory transepithelial sodium transport may also facilitate pulmonary oedema in humans.
Mots-clé
*Amiloride Animals Epithelial Sodium Channel *Genetic Predisposition to Disease Humans Membrane Potentials/physiology Mice Mice, Knockout Mice, Transgenic Pulmonary Edema/*genetics/*metabolism Respiratory Mucosa/*metabolism Sodium Channels/biosynthesis/*deficiency/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:42
Dernière modification de la notice
20/08/2019 15:58
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