Chronic Furosemide Administration Alters Abundance of Sodium Transporters in Rat Kidney.
- Author:
Yoon Kyu OH
1
;
Ki Young NA
;
Jay Wook LEE
;
Hye Ryun CHANG
;
Young Sun PARK
;
Junghwan PARK
;
Kwon Wook JOO
;
Gheun Ho KIM
;
Jung Sang LEE
;
Jin Suk HAN
Author Information
1. Department of Internal Medicine, Eulji Medical College, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Furosemide;
NKCC2;
NCC;
ENaC
- MeSH:
Absorption;
Aldosterone;
Animals;
Body Weight;
Creatinine;
Drinking Water;
Epithelial Sodium Channels;
Extremities;
Furosemide*;
Immunoblotting;
Immunohistochemistry;
Kidney*;
Nephrons;
Rats*;
Rats, Sprague-Dawley;
Sodium*
- From:Korean Journal of Nephrology
2003;22(2):195-204
- CountryRepublic of Korea
- Language:Korean
-
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.
