TY - JOUR
T1 - Altered expression of major renal Na transporters in rats with unilateral ureteral obstruction
AU - Li, Chunling
AU - Wang, Weidong
AU - Kwon, Tae Hwan
AU - Knepper, Mark A.
AU - Nielsen, Søren
AU - Frøkiær, Jørgen
PY - 2003/1/1
Y1 - 2003/1/1
N2 - 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 Frøkiær 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 μmol/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-Pi 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 μl·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.
AB - 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 Frøkiær 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 μmol/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-Pi 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 μl·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.
KW - Collecting duct
KW - Distal convoluted tubule
KW - Obstructive nephropathy
KW - Proximal tubule
KW - Sodium excretion
KW - Thick ascending limb of Henle's loop
UR - http://www.scopus.com/inward/record.url?scp=0037214009&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00272.2002
DO - 10.1152/ajprenal.00272.2002
M3 - Article
C2 - 12388400
AN - SCOPUS:0037214009
SN - 1931-857X
VL - 284
SP - F155-F166
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 1 53-1
ER -