Thiazolidinedione-induced fluid retention is independent of collecting duct αENaC activity

Volker Vallon, Edith Hummler, Timo Rieg, Oleh Pochynyuk, Vladislav Bugaj, Jana Schroth, Georges Dechenes, Bernard Rossier, Robyn Cunard, James Stockand

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Thiazolidinediones are agonists of peroxisome proliferator-activated receptor γ) 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 α 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 thiazo- lidinedione-induced fluid retention.

Original languageEnglish (US)
Pages (from-to)721-729
Number of pages9
JournalJournal of the American Society of Nephrology
Volume20
Issue number4
DOIs
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Nephrology

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    Vallon, V., Hummler, E., Rieg, T., Pochynyuk, O., Bugaj, V., Schroth, J., Dechenes, G., Rossier, B., Cunard, R., & Stockand, J. (2009). Thiazolidinedione-induced fluid retention is independent of collecting duct αENaC activity. Journal of the American Society of Nephrology, 20(4), 721-729. https://doi.org/10.1681/ASN.2008040415