title: Urinary concentrating defect in hypothyroid rats: role of sodium, potassium, 2-chloride co-transporter, and aquaporins.
abstract: Hypothyroidism is associated with impaired urinary concentrating ability in humans and animals. The purpose of this study was to examine protein expression of renal sodium chloride and urea transporters and aquaporins in hypothyroid rats (HT) with diminished urinary concentration as compared with euthyroid controls (CTL) and hypothyroid rats replaced with L-thyroxine (HT+T). Hypothyroidism was induced by aminotriazole administration. Body weight, water intake, urine output, solute and urea excretion, serum and urine osmolality, serum creatinine, 24-h creatinine clearance, and fractional excretion of sodium were comparable among the three groups. However, with 36 h of water deprivation, HT rats demonstrated significantly greater urine flow rates and decreased urine and medullary osmolality as compared with CTL and HT+T rats at comparable plasma vasopressin concentrations. Western blot analyses revealed decreased renal protein abundance of transporters, including Na-K-2Cl, Na-K-ATPase, and NHE3, in HT rats as compared with CTL and HT+T rats. Protein abundance of renal AQP1 and urea transporters UTA(1) and UTA(2) did not differ significantly among study groups. There was however a significant decrease in protein abundance of AQP2, AQP3, and AQP4 in HT rats as compared with CTL and HT+T rats. These findings demonstrate a decrease in the medullary osmotic gradient secondary to impaired countercurrent multiplication and downregulation of aquaporins 2, 3, and 4 as contributors to the urinary concentrating defect in the hypothyroid rat.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Denver, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Cadnapaphornchai
authors.forename: Yang-Wook
authors.initials: YW
authors.lastname: Kim
authors.forename: Andrey K
authors.initials: AK
authors.lastname: Gurevich
authors.forename: Sandra N
authors.initials: SN
authors.lastname: Summer
authors.forename: Sandor
authors.initials: S
authors.lastname: Falk
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Thurman
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D000818:Animals; D051398:Aquaporin 1; D051399:Aquaporin 2; D051400:Aquaporin 3; D051401:Aquaporin 4; D051403:Aquaporin 6; D020346:Aquaporins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D007037:Hypothyroidism / Q000378:metabolism*; D007671:Kidney Concentrating Ability / Q000502:physiology*; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D014868:Water Deprivation / Q000502:physiology; D000096982:Urea Transporters
chemical_list: D051398:Aquaporin 1; D051399:Aquaporin 2; D051400:Aquaporin 3; D051401:Aquaporin 4; D051403:Aquaporin 6; D020346:Aquaporins; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D028021:Sodium-Potassium-Chloride Symporters; D000096982:Urea Transporters; C496022:Aqp1 protein, rat; C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; C496032:Aqp4 protein, rat