Altered expression of major renal Na transporters in rats with bilateral ureteral obstruction and release of obstruction.

Abstract

Urinary tract obstruction impairs urinary concentrating capacity and reabsorption of sodium. To clarify the molecular mechanisms of these defects, expression levels of renal sodium transporters were examined in rats with 24-h bilateral ureteral obstruction (BUO) or at day 3 or 14 after release of BUO (BUO-R). BUO resulted in downregulation of type 3 Na+/H+ exchanger (NHE3) to 41 +/- 14%, type 2 Na-Pi cotransporter (NaPi-2) to 26 +/- 6%, Na-K-ATPase to 67 +/- 8%, type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) to 20 +/- 7%, and thiazide-sensitive cotransporter (TSC) to 37 +/- 9%. Immunocytochemistry confirmed downregulation of NHE3, NaPi-2, Na-K-ATPase, BSC-1, and TSC. Consistent with this downregulation, BUO-R was associated with polyuria, reduced urinary osmolality, and increased urinary sodium and phosphate excretion. BUO-R for 3 days caused a persistant downregulation of NHE3 to 53 +/- 10%, NaPi-2 to 57 +/- 9%, Na-K-ATPase to 62 +/- 8%, BSC-1 to 50 +/- 12%, and TSC to 56 +/- 16%, which was associated with a marked reduction in the net renal reabsorption of sodium (616 +/- 54 vs. 944 +/- 24 micromol x min-1 x kg-1; P < 0.05) and phosphate (6.3 +/- 0.9 vs. 13.1 +/- 0.4 micromol x min-1. kg-1; P < 0.05) demonstrating a defect in renal sodium and phosphate reabsorption capacity. Moreover, downregulation of Na-K-ATPase and TSC persisted in BUO-R for 14 days, whereas NHE3, NaPi-2, and BSC-1 were normalized to control levels. In conclusion, downregulation of renal Na transporters in rats with BUO and release of BUO are likely to contribute to the associated urinary concentrating defect, increased urinary sodium excretion, and postobstructive polyuria.

• Authors: Chunling Li, Weidong Wang, Tae-Hwan Kwon, Mark A Knepper, Søren Nielsen, Jørgen Frøkiaer
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 285 Issue 5 Pg. F889-901 (Nov 2003) ISSN: 1931-857X [Print] United States
• PMID: 12865255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carrier Proteins
• Receptors, Drug
• Slc12a1 protein, rat
• Slc12a3 protein, rat
• Slc9a3 protein, rat
• Sodium Chloride Symporters
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers
• Sodium-Phosphate Cotransporter Proteins
• Sodium-Phosphate Cotransporter Proteins, Type I
• Sodium-Phosphate Cotransporter Proteins, Type II
• Sodium-Potassium-Chloride Symporters
• Solute Carrier Family 12, Member 1
• Solute Carrier Family 12, Member 3
• Symporters
• thiazide receptor
• Water
• Sodium
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Carrier Proteins (metabolism)
• Down-Regulation
• Kidney (metabolism)
• Male
• Rats
• Rats, Wistar
• Receptors, Drug (metabolism)
• Sodium (metabolism)
• Sodium Chloride Symporters
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers (metabolism)
• Sodium-Phosphate Cotransporter Proteins
• Sodium-Phosphate Cotransporter Proteins, Type I
• Sodium-Phosphate Cotransporter Proteins, Type II
• Sodium-Potassium-Chloride Symporters (metabolism)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Solute Carrier Family 12, Member 1
• Solute Carrier Family 12, Member 3
• Symporters (metabolism)
• Ureteral Obstruction (metabolism)
• Water (metabolism)