Angiotensin II AT1 Receptor Blockade Changes Expression of Renal Sodium Transporters in Rats with Chronic Renal Failure.
10.3346/jkms.2005.20.2.248
- Author:
Eun Jung KIM
1
;
Yong Wuk JUNG
;
Tae Hwan KWON
Author Information
1. Department of Physiology, School of Medicine, Dongguk University, Kyungju, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Angiotensin II;
Aquaporins;
BSC-1 Protein, rat;
Kidney Failure;
Vasopressins
- MeSH:
Angiotensin II Type 1 Receptor Blockers;
Animals;
Aquaporins/genetics;
Benzimidazoles/*pharmacology;
Blood Urea Nitrogen;
Kidney Failure, Chronic/drug therapy/*metabolism;
Male;
Organ Size/drug effects;
Rats;
Rats, Sprague-Dawley;
Receptors, Drug/*genetics;
Research Support, Non-U.S. Gov't;
Sodium-Hydrogen Antiporter/*genetics;
Sodium-Potassium-Chloride Symporters/*genetics;
Symporters/*genetics;
Tetrazoles/*pharmacology
- From:Journal of Korean Medical Science
2005;20(2):248-255
- CountryRepublic of Korea
- Language:English
-
Abstract:
We aimed to examine the effects of angiotensin II AT1 receptor blocker on the expression of major renal sodium transporters and aquaporin-2 (AQP2) in rats with chronic renal failure (CRF). During 2 wks after 5/6 nephrectomy or sham operation, both CRF rats (n=10) and sham-operated control rats (n=7) received a fixed amount of low sodium diet and had free access to water. CRF rats (n=10) were divided into two groups which were either candesartan-treated (CRF-C, n=4) or vehicletreated (CRF-V, n=6). Both CRF-C and CRF-V demonstrated azotemia, decreased GFR, polyuria, and decreased urine osmolality compared with sham-operated rats. When compared with CRF-V, CRF-C was associated with significantly higher BUN levels and lower remnant kidney weight. Semiquantitative immunoblotting demonstrated decreased AQP2 expression in both CRF-C (54% of control levels) and CRF-V (57%), whereas BSC-1 expression was increased in both CRF groups. Particularly, CRF-C was associated with higher BSC-1 expression (611%) compared with CRF-V (289%). In contrast, the expression of NHE3 (25%) and TSC (27%) was decreased in CRF-C, whereas no changes were observed in CRF-V. In conclusion, 1) candesartan treatment in an early phase of CRF is associated with decreased renal hypertrophy and increased BUN level; 2) decreased AQP2 level in CRF is likely to play a role in the decreased urine concentration, and the downregulation is not altered in response to candesartan treatment; 3) candesartan treatment decreases NHE3 and TSC expression; and 4) an increase of BSC-1 is prominent in candesartan-treated CRF rats, which could be associated with the increased delivery of sodium and water to the thick ascending limb.
