Renoprotective effects of mineralocorticoid receptor blockade in heminephrectomized (pro)renin receptor transgenic rats

Yuki Mizuguchi, Atsuhiro Ichihara, Yasufumi Seki, Mariyo Sakoda, Asako Kurauchi-Mito, Tatsuya Narita, Kenichiro Kinouchi, Kanako Bokuda, Hiroshi Itoh

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)569-573
Number of pages5
JournalClinical and Experimental Pharmacology and Physiology
Volume37
Issue number5-6
DOIs
Publication statusPublished - 2010

Fingerprint

Transgenic Rats
Mineralocorticoid Receptors
Renin
Aldosterone
Sodium
Diet
Messenger RNA
Nephrectomy
Dietary Sodium
Tight Junctions
Proteinuria
Salts
Diaphragm
Reverse Transcription
eplerenone
Arterial Pressure
Proteins

Keywords

  • (pro)renin receptor
  • Aldosterone
  • Dietary salt
  • Eplerenone
  • Heminephrectomy
  • Proteinuria
  • Slit diaphragm proteins

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology
  • Medicine(all)

Cite this

Renoprotective effects of mineralocorticoid receptor blockade in heminephrectomized (pro)renin receptor transgenic rats. / Mizuguchi, Yuki; Ichihara, Atsuhiro; Seki, Yasufumi; Sakoda, Mariyo; Kurauchi-Mito, Asako; Narita, Tatsuya; Kinouchi, Kenichiro; Bokuda, Kanako; Itoh, Hiroshi.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 37, No. 5-6, 2010, p. 569-573.

Research output: Contribution to journalArticle

Mizuguchi, Yuki ; Ichihara, Atsuhiro ; Seki, Yasufumi ; Sakoda, Mariyo ; Kurauchi-Mito, Asako ; Narita, Tatsuya ; Kinouchi, Kenichiro ; Bokuda, Kanako ; Itoh, Hiroshi. / Renoprotective effects of mineralocorticoid receptor blockade in heminephrectomized (pro)renin receptor transgenic rats. In: Clinical and Experimental Pharmacology and Physiology. 2010 ; Vol. 37, No. 5-6. pp. 569-573.
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AU - Sakoda, Mariyo

AU - Kurauchi-Mito, Asako

AU - Narita, Tatsuya

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