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Thiazolidinedione-Induced Fluid Retention Is Independent of Collecting Duct αENaC Activity
- Source :
- Journal of the American Society of Nephrology : JASN
- Publication Year :
- 2009
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2009.
-
Abstract
- 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.
- Subjects :
- Epithelial sodium channel
medicine.medical_specialty
Patch-Clamp Techniques
medicine.drug_class
030232 urology & nephrology
Weight Gain
Rosiglitazone
Mice
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Animals
Patch clamp
Kidney Tubules, Collecting
Thiazolidinedione
Epithelial Sodium Channels
Receptor
030304 developmental biology
Kidney Medulla
0303 health sciences
Kidney
Pioglitazone
Chemistry
Biological activity
General Medicine
Basic Research
medicine.anatomical_structure
Endocrinology
Nephrology
Thiazolidinediones
medicine.drug
Subjects
Details
- ISSN :
- 10466673
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Nephrology
- Accession number :
- edsair.doi.dedup.....8bec148beb3c15e0e12bca0bee6c300d