Changes of Urinary Acidification and Collecting Duct H(+)-ATPase Abundance in Response to Chronic Diuretic Administration.
- Author:
Gheun Ho KIM
1
;
Ki Young NA
;
Jin Suk HAN
;
Yoon Kyu OH
;
Jung Sang LEE
;
Kwon Wook JOO
;
Jae Ho EARM
Author Information
1. Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea. kimgh@hallym.or.kr
- Publication Type:Original Article
- Keywords:
Furosemide;
Hydrochlorothiazide;
NHE3;
H(+)-ATPase;
Urinary acidification
- MeSH:
Adenosine Triphosphatases;
Aldosterone;
Alkalosis;
Ammonium Compounds;
Animals;
Antibodies;
Body Weight;
Creatinine;
Diuretics;
Drinking;
Extremities;
Furosemide;
Hydrochlorothiazide;
Hydrogen-Ion Concentration;
Immunoblotting;
Infusions, Subcutaneous;
Kidney;
Nephrons;
Proton-Translocating ATPases*;
Protons;
Rats;
Rats, Sprague-Dawley;
Water
- From:Korean Journal of Nephrology
2002;21(2):222-231
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Commonly used diuretics such as furosemide and hydrochlorothiazide may cause metabolic alkalosis by increasing proton secretion from distal nephron. We evaluated changes in urinary acidification and abundance of proton-secreting transporters in response to chronic subcutaneous infusion of diuretics. METHODS: Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day furoemide or hydrochlorothiazide 7.5 mg/day for 7 days. All animals were offered tap water and a solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. RESULTS: Compared with vehicle-infused controls, diuretic and natriuretic responses were evident from furosemide or hydrochlorothiazide infusion. However, there were no changes in body weight, serum aldosterone and creatinine clearance between diuretic- infused(n=6) and control(n=6) rats. In both furosemide-infused and hydrochlorothiazide-infused rats, urine pH was significantly lowered compared with controls. Furosemide-infused rats showed significantly larger excretion of urinary ammonium. Semiquantitative immunoblotting was carried out from rat kidneys to investigate abundance of proximal tubule or medullary thick ascending limb Na(+)/H(+) exchanger type 3(NHE3) and collecting duct H(+)- ATPase using specific polyclonal antibodies to NHE3 and H(+)-ATPase B1 subunit, respectively. The abundance of NHE3 from cortical homogenates was not changed by either furosemide or hydrochlorothiazide infusion. However, the abundance of NHE3 from outer medullary homogenates was increased by furosemide infusion. The H(+)-ATPase B1 subunit abundance was increased by furosemide or hydrochlorothiazide infusion in both cortical and outer medullary homogenates. CONCLUSION: These increases in the abundance of proton-secreting transporters may account for the enhanced distal urinary acidification in response to chronic diuretic administration.
