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.