Korean J Nephrol.
2003 Mar;22(2):195-204.
Chronic Furosemide Administration Alters Abundance of Sodium Transporters in Rat Kidney
- Affiliations
-
- 1Department of Internal Medicine, Eulji Medical College, Seoul, Korea.
- 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. jshan@snu.ac.kr
- 3Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
Abstract
- BACKGROUND
Furosemide inhibit NaCl absorption in the thick ascending limb and produce an increase in distal delivery of Na+. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic furosemide infusion is associated with compensatory increases in the abundance of Na+ transporters in distal nephron. METHODS: Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day of furosemide(n=6) with simultaneous administration of 0.8% NaCl and 0.1% KCl in drinking water for 7 days.
RESULTS
Compared with vehicle infused controls, urine volume and urine sodium amount were increased. However, there were no differences in body weight, serum aldosterone, and creatinine clearance. The abundance of Na+-K+-2Cl- cotransporter after furosemide infusion was increased in cortex (151+/-10 vs. 100+/-10%, p< 0.05) and outer medulla (122+/-5 vs. 100+/-3%, p< 0.01). In furosemide infusion group, the abundance of all three subunits of epithelial sodium channel (ENaC) was increased both in cortex (alpha: 187+/-25 vs. 100+/-17%, p< 0.05; beta: 155+/-8 vs. 100+/-15%, p< 0.05; gamma: 168+/-16 vs. 100+/-9%, p< 0.05) and outer medulla (alpha: 171+/-27 vs. 100+/-17%, p< 0.05; beta: 986+/-91 vs. 100+/-33%, p< 0.01; gamma: 242+/-24 vs. 100+/-22%, p< 0.01). Consistent with these results, ENaC beta-subuint immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with furosemide treatment.
CONCLUSION
These increases in the abundance of ENaC protein may account for the generation of diuretic tolerance.
Keyword
- Furosemide; NKCC2; NCC; ENaC
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Changes of Urinary Acidification and Collecting Duct H(+)-ATPase Abundance in Response to Chronic Diuretic Administration
- Loop Diuretics in Clinical Practice
- Effect of Furosemide on the Serum Concentration of Sodium and Osmolality after Transurethral Resection of Prostate
- Altered Regulation of Renal Aquaporins and Sodium Transporters in Experimental Chronic Renal Failure
- Mechanisms of Diuretic Resistance and Tolerance
