title: Neonatal ureteral obstruction alters expression of renal sodium transporters and aquaporin water channels.
abstract: BACKGROUND
  Congenital urinary tract obstruction is a common cause of renal insufficiency in the neonate and during infancy. Recently, we demonstrated that ureteral obstruction in adult rats is associated with reduction in the abundance of renal aquaporins (AQPs) and renal sodium transporters, which paralleled an impaired urinary concentrating capacity.
  
  
  METHODS
  In the present study, renal handling of sodium and water, together with the expression of renal aquaporins and major renal sodium transporters, was examined in rats with neonatally induced partial unilateral ureteral obstruction (PUUO) within the first 48 hours of life to clarify the molecular mechanisms involved in the tubular functional defects in response to congenital obstruction. Rats were then followed for 12 or 24 weeks.
  
  
  RESULTS
  Neonatal PUUO caused a progressive reduction in single kidney glomerular filtration rate (SKGFR) on the obstructed side to 43% of controls at 12 weeks (115 +/- 28 vs. 267 +/- 36 microL/min/100g bw, P < 0.05), and 31% of controls at 24 weeks (106 +/- 24 vs. 343 +/- 41 microL/min/100g bw, P < 0.05). Na-K-ATPase abundance was decreased in the obstructed kidney compared with the nonobstructed kidney at 24 weeks (79 +/- 6%, P < 0.05), and the abundance of bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) located to the medullary thick ascending limb (mTAL) of the obstructed kidney was significantly reduced both at 12 weeks (42 +/- 10%, P < 0.05) and 24 weeks (50 +/- 10%, P < 0.05). Immunohistochemistry confirmed down-regulation of BSC-1 both at 12 and 24 weeks after onset of obstruction. Consistent with this, sodium excretion from the obstructed kidney was increased at 12 weeks (0.13 +/- 0.03 vs. 0.04 +/- 0.01 micromol/min/100g bw, P < 0.05), and persisted 24 weeks after onset of PUUO (0.15 +/- 0.02 vs. 0.06 +/- 0.01 micromol/min/100g bw, P < 0.05). AQP2 abundance in the collecting duct was also reduced both at 12 weeks (68 +/- 5%, P < 0.05) and at 24 weeks (69 +/- 13%, P < 0.05). Consistent with this, solute-free water reabsorption was decreased in the obstructed kidney at 12 weeks (0.61 +/- 0.42 vs. 1.97 +/- 0.63 microL/min/100g bw, P < 0.05) and remained decreased after 24 weeks of PUUO (0.42 +/- 0.04 vs. 1.56 +/- 0.39 microL/min/100g bw, P < 0.05).
  
  
  CONCLUSIONS
  Major sodium transporters and aquaporins in the obstructed kidney are down-regulated in response to neonatally induced PUUO, which indicates that these transporters may play a crucial role for the persistent reduction in renal handling of sodium and water in response to PUUO.
authors.affiliation: Institute of Experimental Clinical Research, Aarhus University, Aarhus, Denmark.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Shi
authors.forename: Chunling
authors.initials: C
authors.lastname: Li
authors.forename: Klaus
authors.initials: K
authors.lastname: Thomsen
authors.forename: Troels Munch
authors.initials: TM
authors.lastname: Jørgensen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Knepper
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Jens Christian
authors.initials: JC
authors.lastname: Djurhuus
authors.forename: Jørgen
authors.initials: J
authors.lastname: Frøkiaer
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D051399:Aquaporin 2; D020346:Aquaporins / Q000378:metabolism*; D018450:Disease Progression; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D064466:Solute Carrier Family 12, Member 1; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine
chemical_list: C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D020346:Aquaporins; C578716:Slc12a1 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D000254:Sodium-Potassium-Exchanging ATPase