Angiotensin II AT1 receptor blockade changes expression of renal sodium transporters in rats with chronic renal failure.
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.
Kim
Eun-Jung
EJ
Department of Physiology, School of Medicine, Dongguk University, Kyungju, Korea.
Jung
Yong-Wuk
YW
Kwon
Tae-Hwan
TH
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*
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