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1 University of Aarhus, The Water and Salt Research Center, Aarhus, Denmark; Aarhus University Hospital-Skejby, Institute of Clinical Medicine, Aarhus, Denmark
2 Renal Division, Department of Medicine, Emory University, Atlanta, Georgia, USA
3 University of Aarhus, The Water and Salt Research Center, Aarhus, Denmark; Department of Cell Biology, Institute of Anatomy, Aarhus, Denmark
4 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
5 University of Aarhus, The Water and Salt Research Center, Aarhus, Denmark; Aarhus University Hospital-Skejby, Institute of Clinical Medicine, Aarhus, Denmark; Aarhus University Hospital-Skejby, Department of Clinical Physiology, Aarhus, Denmark
* To whom correspondence should be addressed. E-mail: jf{at}iekf.au.dk.
Urea plays an important role in the urine concentrating capacity. Renal inner medullary (IM) urea transporter expression was examined in rats with bilateral (BUO) or unilateral ureteral obstruction (UUO). BUO (24 hour) was associated with markedly increased plasma urea (42.4 ± 1.0 vs. 5.2 ± 0.2 mmol/l) and a significant decease in expression of UT-A1 (28 ± 8 % of sham levels); UT-A3 (45 ± 11%) and UT-B (70 ± 8%). Immunocytochemistry confirmed downregulation of UT-A1 and UT-A3 in IM collecting duct and UT-B in the descending vasa recta. Three days after release of BUO, UT-A1, UT-A3 and UT-B remained significantly downregulated (UT-A1: 37 ± 6%; UT-A3: 25 ± 6%; and UT-B: 10 ± 5% of sham levels; p<0.05) concurrent with a persistent polyuria and a marked reduction in solute-free water reabsorption (115 ± 11 vs. 196 ± 8 µl/min/kg, p<0.05). Moreover, fourteen days after release of BUO, total UT-A1, UT-A3 and UT-B remained decreased significantly compared with shamoperated controls and urine urea remained reduced (588 ± 43 vs. 1150 ± 94 mmol/l). Consistent with increased levels of plasma urea 24 hours after onset of UUO (7.4 ± 0.3 vs. 4.8 ± 0.3 mmol/l), the protein abundance of UT-A1, UT-A3 and UT-B in IM were markedly reduced in the obstructed kidney, which was confirmed by immunocytochemistry. In the non-obstructed kidney the expression of urea transporters did not change. In conclusion, reduced expression of UT-A1, UT-A3 and UT-B levels in both BUO and UUO rats suggest that urea transporters play important roles in the impaired urine concentrating capacity in response to urinary tract obstruction.
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