PPARγ Agonist-Induced Fluid Retention Depends on αENaC Expression in Connecting Tubules.

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Serval ID
serval:BIB_8DEAE0FC9B39
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PPARγ Agonist-Induced Fluid Retention Depends on αENaC Expression in Connecting Tubules.
Journal
Nephron. Physiology
Author(s)
Fu Y., Gerasimova M., Batz F., Kuczkowski A., Alam Y., Sanders P.W., Ronzaud C., Hummler E., Vallon V.
ISSN
1660-2137 (Electronic)
ISSN-L
1660-2110
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
129
Number
1
Pages
68-74
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
BACKGROUND/AIMS: Thiazolidinediones (TZDs, like rosiglitazone (RGZ)) are peroxisome proliferator-activated receptor γ (PPARγ) agonists used to treat type 2 diabetes. Clinical limitations include TZD-induced fluid retention and body weight (BW) increase, which are inhibited by amiloride, an epithelial-sodium channel (ENaC) blocker. RGZ-induced fluid retention is maintained in mice with αENaC knockdown in the collecting duct (CD). Since ENaC in the connecting tubule (CNT) rather than in CD appears to be critical for normal NaCl retention, we aimed to further explore the role of ENaC in CNT in RGZ-induced fluid retention.
METHODS: Mice with conditional inactivation of αENaC in both CNT and CD were used (αENaC lox/lox AQP2-Cre; 'αENaC-CNT/CD-KO') and compared with littermate controls (αENaC lox/lox mice; 'WT'). BW was monitored and total body water (TBW) and extracellular fluid volume (ECF) were determined by bioelectrical impedance spectroscopy (BIS) before and after RGZ (320 mg/kg diet for 10 days).
RESULTS: On regular NaCl diet, αENaC-CNT/CD-KO had normal BW, TBW, ECF, hematocrit, and plasma Na(+), K(+), and creatinine, associated with an increase in plasma aldosterone compared with WT. Challenging αENaC-CNT/CD-KO with a low NaCl diet unmasked impaired NaCl and K homeostasis, consistent with effective knockdown of αENaC. In WT, RGZ increased BW (+6.1%), TBW (+8.4%) and ECF (+10%), consistent with fluid retention. These changes were significantly attenuated in αENaC-CNT/CD-KO (+3.4, 1.3, and 4.3%).
CONCLUSION: Together with the previous studies, the current results are consistent with a role of αENaC in CNT in RGZ-induced fluid retention, which dovetails with the physiological relevance of ENaC in this segment. © 2014 S. Karger AG, Basel.
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2015 16:21
Last modification date
17/09/2020 8:21
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