Thiazolidinedione-induced Fluid Retention is Independent of Collecting Duct AlphaENaC Activity

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2009 Jan 23

PMID 19158355

Citations 48

Authors

Volker Vallon

Edith Hummler

Timo Rieg

Oleh Pochynyuk

Vladislav Bugaj

Jana Schroth

Georges Dechenes

Bernard Rossier

Robyn Cunard

James Stockand

Affiliations

Soon will be listed here.

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.

Citing Articles

Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism.

Hsu C, Hsuan C, Liao D, Chang J, Chang A, Hee S Life (Basel). 2023; 13(4).

PMID: 37109553 PMC: 10144651. DOI: 10.3390/life13041024.

Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes.

Subash-Babu P, Abdulaziz AlSedairy S, Binobead M, Alshatwi A Metabolites. 2023; 13(2).

PMID: 36837888 PMC: 9965038. DOI: 10.3390/metabo13020269.

PPARG agonist pioglitazone influences diurnal kidney medulla mRNA expression of core clock, inflammation-, and metabolism-related genes disrupted by reverse feeding in mice.

Izmailova O, Kabaliei A, Shynkevych V, Shlykova O, Kaidashev I Physiol Rep. 2022; 10(23):e15535.

PMID: 36511486 PMC: 9746034. DOI: 10.14814/phy2.15535.

Drug repurposing in autosomal dominant polycystic kidney disease: back to the future with pioglitazone.

Mao Z, Valluru M, Ong A Clin Kidney J. 2021; 14(7):1715-1718.

PMID: 34221378 PMC: 8243263. DOI: 10.1093/ckj/sfab062.

Role of the Peroxisome Proliferator Activated Receptors in Hypertension.

Fang S, Livergood M, Nakagawa P, Wu J, Sigmund C Circ Res. 2021; 128(7):1021-1039.

PMID: 33793338 PMC: 8020861. DOI: 10.1161/CIRCRESAHA.120.318062.

References

Marples D, Christensen S, Christensen E, Ottosen P, Nielsen S . Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla. J Clin Invest. 1995; 95(4):1838-45. PMC: 295720. DOI: 10.1172/JCI117863. View

Light D, McCann F, Keller T, Stanton B . Amiloride-sensitive cation channel in apical membrane of inner medullary collecting duct. Am J Physiol. 1988; 255(2 Pt 2):F278-86. DOI: 10.1152/ajprenal.1988.255.2.F278. View

Rieg T, Pothula K, Schroth J, Satriano J, Osswald H, Schnermann J . Vasopressin regulation of inner medullary collecting ducts and compensatory changes in mice lacking adenosine A1 receptors. Am J Physiol Renal Physiol. 2008; 294(3):F638-44. DOI: 10.1152/ajprenal.00344.2007. View

Parulkar A, Pendergrass M, Lee T, Fonseca V . Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med. 2001; 134(1):61-71. DOI: 10.7326/0003-4819-134-1-200101020-00014. View

Marx N, Duez H, Fruchart J, Staels B . Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells. Circ Res. 2004; 94(9):1168-78. DOI: 10.1161/01.RES.0000127122.22685.0A. View

Meneton P, Loffing J, Warnock D . Sodium and potassium handling by the aldosterone-sensitive distal nephron: the pivotal role of the distal and connecting tubule. Am J Physiol Renal Physiol. 2004; 287(4):F593-601. DOI: 10.1152/ajprenal.00454.2003. View

Nesto R, Bell D, Bonow R, Fonseca V, Grundy S, Horton E . Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation. 2003; 108(23):2941-8. DOI: 10.1161/01.CIR.0000103683.99399.7E. View

Kemendy A, Kleyman T, Eaton D . Aldosterone alters the open probability of amiloride-blockable sodium channels in A6 epithelia. Am J Physiol. 1992; 263(4 Pt 1):C825-37. DOI: 10.1152/ajpcell.1992.263.4.C825. View

Kapadia R, Yi J, Vemuganti R . Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists. Front Biosci. 2007; 13:1813-26. PMC: 2734868. DOI: 10.2741/2802. View

10.

Chen L, Yang B, McNulty J, Clifton L, Binz J, Grimes A . GI262570, a peroxisome proliferator-activated receptor {gamma} agonist, changes electrolytes and water reabsorption from the distal nephron in rats. J Pharmacol Exp Ther. 2004; 312(2):718-25. DOI: 10.1124/jpet.104.074088. View

11.

Nofziger C, Chen L, Shane M, Smith C, Brown K, Blazer-Yost B . PPARgamma agonists do not directly enhance basal or insulin-stimulated Na(+) transport via the epithelial Na(+) channel. Pflugers Arch. 2005; 451(3):445-53. DOI: 10.1007/s00424-005-1477-4. View

12.

Light D, Schwiebert E, Karlson K, Stanton B . Atrial natriuretic peptide inhibits a cation channel in renal inner medullary collecting duct cells. Science. 1989; 243(4889):383-5. DOI: 10.1126/science.2463673. View

13.

Zanchi A, Chiolero A, Maillard M, Nussberger J, Brunner H, Burnier M . Effects of the peroxisomal proliferator-activated receptor-gamma agonist pioglitazone on renal and hormonal responses to salt in healthy men. J Clin Endocrinol Metab. 2004; 89(3):1140-5. DOI: 10.1210/jc.2003-031526. View

14.

FRINDT G, Sackin H, Palmer L . Whole-cell currents in rat cortical collecting tubule: low-Na diet increases amiloride-sensitive conductance. Am J Physiol. 1990; 258(3 Pt 2):F562-7. DOI: 10.1152/ajprenal.1990.258.3.F562. View

15.

Vasudevan A, Balasubramanyam A . Thiazolidinediones: a review of their mechanisms of insulin sensitization, therapeutic potential, clinical efficacy, and tolerability. Diabetes Technol Ther. 2005; 6(6):850-63. DOI: 10.1089/dia.2004.6.850. View

16.

Gardiner S, Nunez D, Baer P, Brown K, Bennett T . Regional hemodynamic effects of the N-(2-benzoylphenyl)-L-tyrosine peroxisome proliferator-activated receptor-gamma ligand, GI 262570 [(S)-2-(2-benzoylphenylamino)-3-[4-[2-(5-methyl-2-phenyl-2-oxazol-4-yl)ethoxy]phenyl]propionic acid], in conscious.... J Pharmacol Exp Ther. 2004; 310(3):1226-33. DOI: 10.1124/jpet.104.068817. View

17.

Staruschenko A, Pochynyuk O, Vandewalle A, Bugaj V, Stockand J . Acute regulation of the epithelial Na+ channel by phosphatidylinositide 3-OH kinase signaling in native collecting duct principal cells. J Am Soc Nephrol. 2007; 18(6):1652-61. DOI: 10.1681/ASN.2007010020. View

18.

Buchanan T, Meehan W, Jeng Y, Yang D, Chan T, Nadler J . Blood pressure lowering by pioglitazone. Evidence for a direct vascular effect. J Clin Invest. 1995; 96(1):354-60. PMC: 185207. DOI: 10.1172/JCI118041. View

19.

Li D, Wei Y, Babilonia E, Wang Z, Wang W . Inhibition of phosphatidylinositol 3-kinase stimulates activity of the small-conductance K channel in the CCD. Am J Physiol Renal Physiol. 2005; 290(4):F806-12. PMC: 2847509. DOI: 10.1152/ajprenal.00352.2005. View

20.

Guan Y, Hao C, Cha D, Rao R, Lu W, Kohan D . Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption. Nat Med. 2005; 11(8):861-6. DOI: 10.1038/nm1278. View