Ureter obstruction alters expression of renal acid-base transport proteins in rat kidney

Abstract

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.