Oxidative stress-induced glomerular mineralocorticoid receptor activation limits the benefit of salt reduction in Dahl salt-sensitive rats

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27464
Title
Oxidative stress-induced glomerular mineralocorticoid receptor activation limits the benefit of salt reduction in Dahl salt-sensitive rats
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Description

Abstract
BACKGROUND:

Mineralocorticoid receptor (MR) antagonists attenuate renal injury in salt-sensitive hypertensive rats with low plasma aldosterone levels. We hypothesized that oxidative stress causes MR activation in high-salt-fed Dahl salt-sensitive rats. Furthermore, we determined if MR activation persisted and induced renal injury, even after switching from a high- to a normal-salt diet.
METHODS AND FINDINGS:

High-salt feeding for 4 weeks increased dihydroethidium fluorescence (DHE, an oxidant production marker), p22phox (a NADPH oxidase subunit) and serum and glucocorticoid-regulated kinase-1 (SGK1, an MR transcript) in glomeruli, compared with normal-salt feeding, and these changes persisted 4 weeks after salt withdrawal. Tempol treatment (0.5 mmol/L) during high-salt feeding abolished the changes in DHE fluorescence, p22phox and SGK1. Dietary salt reduction after a 4-week high-salt diet decreased both blood pressure and proteinuria, but was associated with significantly higher proteinuria than in normal control rats at 4 weeks after salt reduction. Administration of tempol during high-salt feeding, or eplerenone, an MR antagonist (100 mg/kg/day), started after salt reduction, recovered proteinuria to normal levels at 4 weeks after salt reduction. Paraquat, a reactive oxygen species generator, enhanced MR transcriptional activity in cultured rat mesangial cells and mouse podocytes.
CONCLUSIONS:

These results suggest that oxidative stress plays an important role in glomerular MR activation in Dahl salt-sensitive rats. Persistent MR activation even after reducing salt intake could limit the beneficial effects of salt restriction.

(医博甲581)

Author
著者 北田 研人
著者(ヨミ) キタダ ケント
著者(別表記) Kitada Kento
Publication Title
PLoS ONE
Publication Title Alternative
PLoS One.
Volume
7
Issue
7
Start Page
e41896
End Page
e41896
Publisher
Public Library of Science
Published Date
2012-07-24
ISSN
1932-6203
PMID
22911865
DOI
10.1371/journal.pone.0041896
Resource Type
Thesis or Dissertation
Language
eng
Relation
PMCID: PMC3404044
Resource URL
https://doi.org/10.1371/journal.pone.0041896
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404044/
Rights
Copyright Kitada et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
Publisher's Version DOI: https://doi.org/10.1371/journal.pone.0041896
Text Version
ETD
Grant ID
博甲第581号
Grant Date
2014-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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