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

Abstract
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/kgH(2)O (controls 1,211 +/- 90 mosmol/kgH(2)O). 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/kgH(2)O), 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.
AuthorsJennifer J Bedford, John P Leader, Rena Jing, Logan J Walker, Janet D Klein, Jeff M Sands, Robert J Walker
JournalAmerican journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 294 Issue 4 Pg. F812-20 (Apr 2008) ISSN: 1931-857X [Print] United States
PMID18216143 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • RNA, Messenger
  • Aquaporin 1
  • Lithium Carbonate
  • Amiloride
  • Lithium
  • Sodium
  • Potassium
Topics
  • Amiloride (therapeutic use)
  • Animals
  • Aquaporin 1 (genetics)
  • Diabetes Insipidus, Nephrogenic (chemically induced, drug therapy)
  • Disease Models, Animal
  • Kidney Medulla (drug effects, pathology)
  • Lithium (metabolism)
  • Lithium Carbonate (toxicity)
  • Male
  • Potassium (metabolism)
  • RNA, Messenger (genetics)
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium (metabolism)

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