2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, G.-H. Articles by Han, J. S. Search for Related Content PubMed PubMed Citation Articles by Kim, G.-H. Articles by Han, J. S. Related Collections Related Articles

Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Gheun-Ho Kim^*, Jay Wook Lee, Yun Kyu Oh, Hye Ryun Chang, Kwon Wook Joo, Ki Young Na, Jae-Ho Earm, Mark A. Knepper^|| and Jin Suk Han

*Department of Internal Medicine and Institute of Biomedical Sciences, Hanyang University College of Medicine, Seoul, Korea; Department of Internal Medicine, Seoul National University, Clinical Research Institute of Seoul National University Hospital, Seoul, Korea; Department of Internal Medicine, Eulji Medical College, Seoul, Korea; Dr Earm’s Dialysis Clinic, Cheongju, Korea; and ^||Laboratory of Kidney and Electrolyte Metabolism, National Institutes of Health, Bethesda, Maryland

Correspondence to Dr. Jin Suk Han, Department of Internal Medicine, Seoul National University College of Medicine, 28, Yongun-dong, Chongno-gu, Seoul, 110-744, South Korea. Phone: +82-2-760-2392; Fax: +82-2-3673-2392; E-mail: jshan{at}snu.ac.kr

Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear. Previous studies have reported that downregulation of aquaporin-2 (AQP2) is important for the development of lithium-induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal papillary osmolality and Na⁺ concentration in Brattleboro rats. For elucidating the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus, whether administration of HCTZ may affect the expression of AQP2 and major renal Na⁺ transporters in Li-induced NDI rats was investigated, using semiquantitative immunoblotting and immunohistochemistry. After feeding male Sprague-Dawley rats Li chloride–containing rat diet for 4 wk, HCTZ or vehicle was infused subcutaneously via osmotic minipump. Urine output was significantly decreased by HCTZ treatment, whereas it was not changed in vehicle-treated rats. Urine osmolality was also higher in HCTZ-treated rats than in vehicle-treated rats. Semiquantitative immunoblotting using whole-kidney homogenates revealed that HCTZ treatment caused a significant partial recovery in AQP2 abundance from Li-induced downregulation. AQP2 immunohistochemistry showed compatible findings with the immunoblot results in both cortex and medulla. The abundances of thiazide-sensitive NaCl co-transporter and -epithelial sodium channel were increased by HCTZ treatment. Notably, HCTZ treatment induced a shift in molecular weight of -epithelial sodium channel from 85 to 70 kD, consistent with previously demonstrated aldosterone stimulation. The upregulation of AQP2 and distal renal Na⁺ transporters in response to HCTZ treatment may account for the antidiuretic action of HCTZ in NDI.

Related Articles

This Month’s Highlights
J. Am. Soc. Nephrol. 2004 15: 2765-2767. [Full Text] [PDF]

This article has been cited by other articles:

				N. Schliebe, R. Strotmann, K. Busse, D. Mitschke, H. Biebermann, L. Schomburg, J. Kohrle, J. Bar, H. Rompler, J. Wess, et al. V2 vasopressin receptor deficiency causes changes in expression and function of renal and hypothalamic components involved in electrolyte and water homeostasis Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1177 - F1190. [Abstract] [Full Text] [PDF]

				W. Fenske, S. Stork, A.-C. Koschker, A. Blechschmidt, D. Lorenz, S. Wortmann, and B. Allolio Value of Fractional Uric Acid Excretion in Differential Diagnosis of Hyponatremic Patients on Diuretics J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 2991 - 2997. [Abstract] [Full Text] [PDF]

				G.-H. Kim, N. W. Choi, J.-Y. Jung, J.-H. Song, C. H. Lee, C. M. Kang, and M. A. Knepper Treating lithium-induced nephrogenic diabetes insipidus with a COX-2 inhibitor improves polyuria via upregulation of AQP2 and NKCC2 Am J Physiol Renal Physiol, April 1, 2008; 294(4): F702 - F709. [Abstract] [Full Text] [PDF]

				J. Nielsen, T.-H. Kwon, J. Frokiaer, M. A. Knepper, and S. Nielsen Lithium-induced NDI in rats is associated with loss of {alpha}-ENaC regulation by aldosterone in CCD Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1222 - F1233. [Abstract] [Full Text] [PDF]

				P. Gross and C. Palm Thiazides: do they kill? Nephrol. Dial. Transplant., November 1, 2005; 20(11): 2299 - 2301. [Full Text] [PDF]

				F. de Mattia, P. J.M. Savelkoul, E.-J. Kamsteeg, I. B.M. Konings, P. van der Sluijs, R. Mallmann, A. Oksche, and P. M.T. Deen Lack of Arginine Vasopressin-Induced Phosphorylation of Aquaporin-2 Mutant AQP2-R254L Explains Dominant Nephrogenic Diabetes Insipidus J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2872 - 2880. [Abstract] [Full Text] [PDF]

				J. Loffing Paradoxical Antidiuretic Effect of Thiazides in Diabetes Insipidus: Another Piece in the Puzzle J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2948 - 2950. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673