Altered expression of major renal Na transporters in rats with unilateral ureteral obstruction.
It has been demonstrated previously that ureteral obstruction was associated with downregulation of renal AQP2 expression and an impaired urinary concentrating capacity (Li C, Wang W, Kwon TH, Isikay L, Wen JG, Marples D, Djurhuus JC, Stockwell A, Knepper MA, Nielsen S, and Frøkiaer J. Am J Physiol Renal Physiol 281: F163-F171, 2001). In the present study, changes in the expression of major renal Na transporters were examined in a rat model with 24 h of unilateral ureteral obstruction (UUO) to clarify the molecular mechanisms of the marked natriuresis seen after release of UUO. Urine collection for 2 h after release of UUO revealed a significant reduction in urinary osmolality, solute-free water reabsorption, and a marked natriuresis (0.29 +/- 0.03 vs. 0.17 +/- 0.03 micromol/min, P < 0.05). Consistent with this, immunoblotting revealed significant reductions in the abundance of major renal Na transporters: type 3 Na(+)/H(+) exchanger (NHE3; 24 +/- 4% of sham-operated control levels), type 2 Na-P(i) cotransporter (NaPi-2; 21 +/- 4%), Na-K-ATPase (37 +/- 4%), type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1; 15 +/- 3%), and thiazide-sensitive Na-Cl cotransporter (TSC; 15 +/- 4%). Immunocytochemistry confirmed the downregulation of NHE3, BSC-1, and TSC in response to obstruction. In nonobstructed contralateral kidneys, a significant reduction in the abundance of inner medullary Na-K-ATPase and cortical NaPi-2 was found. This may contribute to the compensatory increase in urinary production (23 +/- 2 vs. 13 +/- 1 microl x min(-1). kg(-1)) and increased fractional excretion of urinary Na (0.62 +/- 0.03 vs. 0.44 +/- 0.03%, P < 0.05). In conclusion, downregulation of major renal Na transporters in rats with UUO may contribute to the impairment in urinary concentrating capacity and natriuresis after release of obstruction, and reduced levels of Na-K-ATPase and NaPi-2 in the contralateral nonobstructed kidney may contribute to the compensatory increase in water and Na excretion from that kidney during UUO and after release of obstruction.
Li
Chunling
C
The Water and Salt Research Center and Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark.
Wang
Weidong
W
Kwon
Tae-Hwan
TH
Knepper
Mark A
MA
Nielsen
Soren
S
Frøkiaer
Jørgen
J
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D007671:Kidney Concentrating Ability / Q000502:physiology; D007684:Kidney Tubules / Q000378:metabolism; D008138:Loop of Henle / Q000378:metabolism; D008297:Male; D010710:Phosphates / Q000652:urine; D011188:Potassium / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism; D012964:Sodium / Q000652:urine*; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000503:physiopathology*; D014882:Water-Electrolyte Balance / Q000502:physiology
D002352:Carrier Proteins; D010710:Phosphates; D011955:Receptors, Drug; C578716:Slc12a1 protein, rat; C578876:Slc12a3 protein, rat; C000613387:Slc9a3 protein, rat; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium