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Evaluation of water turnover and urine concentration in 11β hydroxysteroid dehydrogenase type 2 knockout (11βHSD2−/−) mice
Author(s) -
Evans Louise Christine,
Kenyon Christopher J,
Mullins John J,
Bailey Matthew A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1079.4
Subject(s) - polyuria , polydipsia , endocrinology , medicine , kidney , aquaporin 2 , chemistry , diabetes mellitus , water channel , mechanical engineering , engineering , inlet
Male 11βHSD2−/− mice and C57Bl/6 controls aged <100d and >180d (n=6–7 per group) were individually housed in metabolic cages and water turnover measured over 4 days after which water was removed for 24hr. In separate studies mice were treated with ddAVP s.c. Mice were culled by decapitation and kidneys and trunk blood collected. Kidneys were formalin fixed and stained with H+E. Renal AQP2 was assessed by western blot. Plasma AVP was measured by radioimmunoassay. At <100d 11βHSD2−/− mice had structurally normal kidneys at both the gross and fine level. However the mice had significant polyuria and polydipsia. Circulating AVP levels were significantly higher in the 11βHSD2−/− mice and AQP2 expression increased following water removal. At 180d polyuria and polydipsia were more severe. Basal AQP2 expression appeared augmented and did not increase with water removal. However, polyuric mice concentrated their urine following ddAVP administration. At >180d medullary atrophy was evident there were signs of tubular dilation. 11βHSD2−/− mice have a deranged water homeostasis. Initially augmented water turnover occurred in the absence of renal injury. At 180d more severe polyuria was associated with medullary atrophy. An upregulation of AQP2 following water deprivation in the <100d mice and a concentration response to ddAVP in polyuric mice suggests a central component to the polyuria. Research supported by the BHF.