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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/F812    most recent 00554.2007v1 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 ISI Web of Science 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 ISI Web of Science (1) Google Scholar Articles by Bedford, J. J. Articles by Walker, R. J. PubMed PubMed Citation Articles by Bedford, J. J. Articles by Walker, R. J.

Amiloride restores renal medullary osmolytes in lithium-induced nephrogenic diabetes insipidus

Departments of ¹Physiology and ²Medicine, University of Otago, Dunedin, New Zealand; and ³Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

Submitted 22 November 2007 ; accepted in final form 11 January 2008

In lithium-induced nephrogenic diabetes insipidus (NDI), alterations in renal medullary osmolyte concentrations have been assumed but never investigated. Amiloride can modify lithium-induced NDI, but the impact of amiloride in lithium-induced NDI on renal medullary osmolytes, aquaporins, and urea transporters is unknown and is the basis of this study. Rats fed lithium (60 mmol/kg dry food) over 4 wk developed NDI. Urine osmolality fell to 287 ± 19 mosmol/kgH₂O (controls 1,211 ± 90 mosmol/kgH₂O). Organic osmolytes in the renal medulla showed significant decreases compared with controls [inositol 221 ± 35 to 85 ± 10 mmol/kg protein; sorbitol 35 ± 9 to 3 ± 1 mmol/kg protein; glycerophosphorylcholine (GPC) 352 ± 80 to 91 ± 20 mmol/kg protein; and glycine betaine 69 ± 11 to 38 ± 38 mmol/kg protein]. Medullary urea content fell from 2,868 ± 624 to 480 ± 117 mmol/kg protein. Concurrent administration of amiloride (0.2 mmol/l) in the drinking water restored urine osmolality (1,132 ± 154 mosmol/kgH₂O), and reduced urine volume. Medullary osmolyte content were restored to control values (inositol, 232 ± 12; sorbitol 32 ± 6; GPC, 244 ± 26; glycine betaine, 84 ± 5 mmol/kg protein). Medullary urea rose to 2,122 ± 305 mmol/kg protein. Reduced AQP2, AQP3, and urea transporter (UT-A1) expression was significantly reversed following amiloride therapy. Data presented here provide further understanding of how amiloride may substantially restore the lithium-induced impaired renal concentrating mechanism.

aquaporin; osmolytes; urea transporter

This article has been cited by other articles:

				J. J. Bedford, S. Weggery, G. Ellis, F. J. McDonald, P. R. Joyce, J. P. Leader, and R. J. Walker Lithium-induced Nephrogenic Diabetes Insipidus: Renal Effects of Amiloride Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1324 - 1331. [Abstract] [Full Text] [PDF]