title: Angiotensin II AT1 receptor blockade changes expression of renal sodium transporters in rats with chronic renal failure.
abstract: We aimed to examine the effects of angiotensin II AT(1) 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 vehicle-treated (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.
authors.affiliation: Department of Physiology, School of Medicine, Dongguk University, Kyungju, Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Kim
authors.forename: Yong-Wuk
authors.initials: YW
authors.lastname: Jung
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kwon
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D051399:Aquaporin 2; D020346:Aquaporins / Q000235:genetics; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001806:Blood Urea Nitrogen; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000235:genetics*; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics*; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics*; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D020346:Aquaporins; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011955:Receptors, Drug; C578716:Slc12a1 protein, rat; C578876:Slc12a3 protein, rat; C000613387:Slc9a3 protein, rat; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D013777:Tetrazoles; C064415:thiazide receptor; C081643:candesartan