Document Detail


Renoprotective effects of mineralocorticoid receptor blockade in heminephrectomized (pro)renin receptor transgenic rats.
MedLine Citation:
PMID:  20082625     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Nephropathy and elevated plasma aldosterone concentrations (PAC) have been observed in (pro)renin receptor transgenic (TG) rats. In the present study, we hypothesized that PAC and/or mineralocorticoid receptor contribute to the nephropathy of TG rats. To test this hypothesis, the effects of a high-sodium (8% NaCl) diet and heminephrectomy on PAC were examined. 2. Feeding of the high-sodium diet for 12 weeks similarly decreased PAC in TG and wild-type (WT) rats. Heminephrectomy further reduced PAC in TG rats fed a high-sodium diet, but had no effect on PAC in WT rats fed a high-sodium diet. 3. Next, the effects of eplerenone (125 mg/kg per day) and dietary salt restriction (0.36% NaCl diet) on proteinuria and renal morphology were examined in rats fed a high-sodium diet or subjected to heminephrectomy. Both eplerenone and dietary sodium restriction significantly reduced the arterial pressure of TG rats, but had no effect in WT rats. In TG rats, treatment with eplerenone significantly decreased urinary protein excretion, but dietary sodium restriction did not. 4. Nephrin and podocin mRNA levels, as determined by real-time quantitative reverse transcription-polymerase chain reaction, were significantly lower in TG rats than in WT rats. In TG rats, eplerenone treatment significantly increased nephrin mRNA levels, but not podocin mRNA levels. Dietary salt restriction significantly increased mRNA levels of both nephrin and podocin. Although zonula occludens (ZO)-1 mRNA levels were similar in both WT and TG rats, eplerenone treatment significantly decreased ZO-1 mRNA levels in TG rats. 5. The results of the present study suggest that the improvement in proteinuria following eplerenone treatment is independent of its effects on sodium balance and may be mediated by effects on the expression of slit diaphragm proteins.
Authors:
Yuki Mizuguchi; Atsuhiro Ichihara; Yasufumi Seki; Mariyo Sakoda; Asako Kurauchi-Mito; Tatsuya Narita; Kenichiro Kinouchi; Kanako Bokuda; Hiroshi Itoh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-17
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  37     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-06-09     Completed Date:  2010-10-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  569-73     Citation Subset:  IM    
Affiliation:
Endocrinology and Anti-Ageing Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
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MeSH Terms
Descriptor/Qualifier:
Aldosterone / blood*
Aldosterone Antagonists / administration & dosage,  pharmacology,  therapeutic use*
Animals
Humans
Kidney Diseases / blood,  etiology,  metabolism,  prevention & control*
Nephrectomy
Rats
Rats, Transgenic
Receptors, Cell Surface / genetics,  physiology*
Receptors, Mineralocorticoid / antagonists & inhibitors*
Sodium Chloride, Dietary / administration & dosage
Spironolactone / administration & dosage,  analogs & derivatives*,  pharmacology,  therapeutic use
Chemical
Reg. No./Substance:
0/Aldosterone Antagonists; 0/Receptors, Cell Surface; 0/Receptors, Mineralocorticoid; 0/Sodium Chloride, Dietary; 0/eplerenone; 0/prorenin receptor; 52-01-7/Spironolactone; 52-39-1/Aldosterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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