Submitted on September 10, 2007
Accepted on May 23, 2008
Ureter obstruction alters expression of renal acid-base transport proteins
in rat kidney
Guixian Wang1, Chunling Li2, Soo-Wan Kim3, Troels Ring4, Jianguo Wen5, Jens Christian Djurhuus6, Weidong Wang7, Soren Nielsen7, and Jorgen Frokiaer8*
1 The Water and Salt Research Center, University of Aarhus, DK-8000 Aarhus C, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University Hospital-Skejby, DK-8200 Aarhus N, Aarhus, Denmark; 3rd Teaching Hospital and Institute of Clinical Medicine, Henan, Zhengzhou University, China, Department of Paediatric Surgery, China
2 University of Aarhus, DK-8000 Aarhus C, The Water and Salt Research, Denmark
3 The Water and Salt Research Center, University of Aarhus, DK-8000 Aarhus C, Aarhus, Denmark; Chonnam National University Medical School, Gwangju, Korea, Department of Internal Medicine, Korea, Republic of
4 Department of Nephrology, Aarhus University Hospital-Aalborg, DK-9000 Aalborg, Denmark
5 Institute of Clinical Medicine, Henan, Zhengzhou University, China, Zhengzhou, China
6 Institute of Clinical Medicine, Aarhus University Hospital-Skejby, DK-8200 Aarhus N, Aarhus, Denmark
7 University of Aarhus, DK-8000 Aarhus C, The Water and Salt Research Center, Denmark
8 The Water and Salt Research Center, University of Aarhus, DK-8000 Aarhus C, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University Hospital-Skejby, DK-8200 Aarhus N, Aarhus, Denmark; Department of Clinical Physiology, Aarhus University Hospital-Skejby, DK-8200 Aarhus N, Aarhus, Denmark
* To whom correspondence should be addressed. E-mail: jf{at}ki.au.dk.
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 significant reductions in the expression of 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%), whereas 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. Release of obstruction increased urinary NH4+ excretion. 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 contributing to the urinary acidification defect after release of obstruction.
