Urinary concentration defect and limited expression of sodium cotransporter, rBSC1, in a rat model of chronic renal failure.
BACKGROUND
Renal urinary concentration is associated with enhanced expression of sodium cotransporter (rBSC1) in thick ascending limb of Henle. Overexpression of rBSC1 was reported recently in hypertrophied nephrons after unilateral nephrectomy (UNX) and in kidney isografts. Since urinary concentration defect and hypertrophy of residual nephrons are major manifestations of chronic renal failure (CRF), we investigated the rBSC1 signals for RNA and protein in a rat model of CRF.


METHODS
Rats underwent 5/6 nephrectomy and examined 8 weeks after operation. rBSC1 mRNA was examined by competitive PCR and in situ hybridization, and rBSC1 protein signals by western blotting and immunohistochemistry. Rats that underwent sham-operation, UNX, or 5/6 nephrectomy followed by a 3-week recovery period (acute renal failure), were used as control. Water intake was restricted for 24 h in subgroups of control and CRF rats.


RESULTS
Microscopic examination showed hypertrophy of residual nephrons in both UNX and CRF rats. Signals for rBSC1 mRNA and protein were enhanced at basal condition only in rats with UNX. Under basal conditions, CRF rats demonstrated low urinary osmolality in spite of high plasma arginine vasopressin levels. Water restriction resulted in increased signals for rBSC1 mRNA and protein and concentration of urine in sham-operated rats, but such increases were absent and urinary concentration was incomplete in CRF rats.


CONCLUSIONS
Compensatory overexpression and upregulation of rBSC1 expression in response to dehydration are both absent in CRF rats. These limitations are thought to be the underlying mechanisms of urinary concentrating defect seen in CRF.
Michimata
Mari
M
Department of Clinical Pharmacology, Tohoku University, Graduate School of Pharmaceutical Science, Sendai, Japan.
Kazama
Itsuro
I
Mizukami
Kazuhiko
K
Araki
Tsutomu
T
Nakamura
Yohsuke
Y
Suzuki
Michiko
M
Wang
Weihua
W
Fujimori
Keise
K
Satomi
Susumu
S
Ito
Sadayoshi
S
Imai
Yutaka
Y
Matsubara
Mitsunobu
M
D000818:Animals; D003681:Dehydration; D006984:Hypertrophy; D007671:Kidney Concentrating Ability; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy; D009399:Nephrons / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism*; D064466:Solute Carrier Family 12, Member 1; D014158:Transcription, Genetic; D016482:Urinalysis
D012333:RNA, Messenger; C578716:Slc12a1 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1