Ureter obstruction alters expression of renal acid-base transport proteins in rat kidney.
Urinary tract obstruction impairs renal function and is often associated with a urinary acidification defect caused by diminished net H+ secretion and/or HCO3- reabsorption. To identify the molecular mechanisms of these defects, protein expression of key acid-base transporters were examined along the renal nephron and collecting duct of kidneys from rats subjected to 24-h bilateral ureteral obstruction (BUO), 4 days after release of BUO (BUO-R), or BUO-R rats with experimentally induced metabolic acidosis (BUO-A). Semiquantitative immunoblotting revealed that BUO caused a significant reduction in the expression of the type 3 Na+/H+ exchanger (NHE3) in the cortex (21 +/- 4%), electrogenic Na+/HCO3- cotransporter (NBC1; 71 +/- 5%), type 1 bumetanide-sensitive Na+-K+-2Cl- cotransporter (NKCC2; 3 +/- 1%), electroneutral Na+/HCO3- cotransporter (NBCn1; 46 +/- 7%), and anion exchanger (pendrin; 87 +/- 2%). The expression of H+-ATPase increased in the inner medullary collecting duct (152 +/- 13%). These changes were confirmed by immunocytochemistry. In BUO-R rats, there was a persistent downregulation of all the acid-base transporters including H+-ATPase. Two days of NH4Cl loading reduced plasma pH and HCO3- levels in BUO-A rats. The results demonstrate that the expression of multiple renal acid-base transporters are markedly altered in response to BUO, which may be responsible for development of metabolic acidosis and contribute to the urinary acidification defect after release of the obstruction.
The Water and Salt Research Center, Aarhus University, Aarhus, Denmark.
Guixian
G
Wang
Chunling
C
Li
Soo Wan
SW
Kim
Troels
T
Ring
Jianguo
J
Wen
Jens Christian
JC
Djurhuus
Weidong
W
Wang
Søren
S
Nielsen
Jørgen
J
Frøkiaer
D000138:Acidosis / Q000209:etiology / Q000378:metabolism*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D006180:Proton-Translocating ATPases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D000076988:Sulfate Transporters; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology
D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; C578716:Slc12a1 protein, rat; C494615:Slc26A4 protein, rat; C422004:Slc4a4 protein, rat; C498902:Slc4a7 protein, rat; C000613387:Slc9a3 protein, rat; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D000076988:Sulfate Transporters; D000643:Ammonium Chloride; D006180:Proton-Translocating ATPases