Thiazolidinedione-induced fluid retention is independent of collecting duct alphaENaC activity.

Détails

ID Serval
serval:BIB_64A9D73DFA71
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Thiazolidinedione-induced fluid retention is independent of collecting duct alphaENaC activity.
Périodique
Journal of the American Society of Nephrology
Auteur(s)
Vallon V., Hummler E., Rieg T., Pochynyuk O., Bugaj V., Schroth J., Dechenes G., Rossier B., Cunard R., Stockand J.
ISSN
1533-3450[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
20
Numéro
4
Pages
721-729
Langue
anglais
Résumé
Thiazolidinediones are agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) that can induce fluid retention and weight gain through unclear mechanisms. To test a proposed role for the epithelial sodium channel ENaC in thiazolidinedione-induced fluid retention, we used mice with conditionally inactivated alphaENaC in the collecting duct (Scnn1a(loxloxCre) mice). In control mice, rosiglitazone did not alter plasma aldosterone levels or protein expression of ENaC subunits in the kidney, but did increase body weight, plasma volume, and the fluid content of abdominal fat pads, and decreased hematocrit. Scnn1a(loxloxCre) mice provided functional evidence for blunted Na+ uptake in the collecting duct, but still exhibited rosiglitazone-induced fluid retention. Moreover, treatment with rosiglitazone or pioglitazone did not significantly alter the open probability or number of ENaC channels per patch in isolated, split-open cortical collecting ducts of wild-type mice. Finally, patch-clamp studies in primary mouse inner medullary collecting duct cells did not detect ENaC activity but did detect a nonselective cation channel upregulated by pioglitazone. These data argue against a primary and critical role of ENaC in thiazolidinedione-induced fluid retention.
Mots-clé
Animals, Epithelial Sodium Channel/drug effects, Epithelial Sodium Channel/physiology, Kidney Medulla/drug effects, Kidney Medulla/physiology, Kidney Tubules, Collecting/drug effects, Kidney Tubules, Collecting/physiology, Mice, Patch-Clamp Techniques, Thiazolidinediones/pharmacology, Weight Gain/drug effects
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/03/2009 10:58
Dernière modification de la notice
20/08/2019 15:20
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