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Chronic candesartan alters expression and activity of NKCC2, NCC, and ENaC in the obese Zucker rat.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2008 May; Vol. 294 (5), pp. F1222-31. Date of Electronic Publication: 2008 Feb 27. - Publication Year :
- 2008
-
Abstract
- The obese Zucker rat reportedly has increased activity of the intrarenal renin-angiotensin-aldosterone system, which conceptually could contribute to elevated salt sensitivity and blood pressure (BP). Our aim was to determine whether there was increased angiotensin II type 1 receptor (AT(1)R)-mediated upregulation of expression or activity of the bumetanide-sensitive Na-K-2Cl cotransporter, the thiazide-sensitive Na-Cl cotransporter (NCC), and/or the epithelial sodium channel (ENaC) in obese vs. lean Zucker rats. Male obese and lean Zucker rats (10-wk old) were fed either 1) control chow (1% NaCl) or 2) chow with candesartan (CAN), an AT(1)R antagonist (25 mg/kg.diet) for 14 wk (n = 8/treatment/body type). BP measured by radiotelemetry, was markedly reduced by CAN ( approximately 20-25 mmHg) in both lean and obese rats with no body-type differences. Obese rats had significantly greater net natriuretic response to single injections of hydrochlorothiazide and benzamil, suggesting increased activity of NCC and ENaC, respectively; however, only the response to benzamil was reduced by CAN. CAN led to a significant reduction in whole kidney levels of NCC and gamma-ENaC (70-kDa band) in both lean and obese rats. However, it significantly increased alpha-ENaC and Na-K-2Cl cotransporter levels, and these increases were greater in obese rats. These studies suggest that relatively increased ENaC, but not NCC activity, in obese rats is due to enhanced AT(1)R activity. CAN attenuated the reduction of several renal transporters in the obese rat kidney. Finally, differences in intrarenal AT(1)R activity do not seem directly responsible for BP differences between lean and obese rats.
- Subjects :
- Amiloride analogs & derivatives
Amiloride pharmacology
Angiotensin II pharmacology
Animals
Biphenyl Compounds
Blood Pressure drug effects
Blotting, Western
Diuretics pharmacology
Furosemide pharmacology
Hypertrophy drug therapy
Hypertrophy etiology
Kidney Tubules, Proximal drug effects
Kidney Tubules, Proximal metabolism
Male
Obesity genetics
Rats
Rats, Zucker
Receptor, Angiotensin, Type 1 metabolism
Renin blood
Sodium-Hydrogen Exchanger 3
Sodium-Hydrogen Exchangers biosynthesis
Sodium-Hydrogen Exchangers genetics
Sodium-Phosphate Cotransporter Proteins, Type IIb biosynthesis
Sodium-Phosphate Cotransporter Proteins, Type IIb genetics
Solute Carrier Family 12, Member 1
Solute Carrier Family 12, Member 3
Angiotensin II Type 1 Receptor Blockers pharmacology
Benzimidazoles pharmacology
Epithelial Sodium Channels biosynthesis
Obesity metabolism
Receptors, Drug biosynthesis
Sodium-Potassium-Chloride Symporters biosynthesis
Symporters biosynthesis
Tetrazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1931-857X
- Volume :
- 294
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 18305093
- Full Text :
- https://doi.org/10.1152/ajprenal.00604.2007