TY - JOUR
T1 - Thiazolidinedione-induced fluid retention is independent of collecting duct αENaC activity
AU - Vallon, Volker
AU - Hummler, Edith
AU - Rieg, Timo
AU - Pochynyuk, Oleh
AU - Bugaj, Vladislav
AU - Schroth, Jana
AU - Dechenes, Georges
AU - Rossier, Bernard
AU - Cunard, Robyn
AU - Stockand, James
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2008040415
DO - 10.1681/ASN.2008040415
M3 - Article
C2 - 19158355
AN - SCOPUS:65249106033
VL - 20
SP - 721
EP - 729
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
SN - 1046-6673
IS - 4
ER -