| Eplerenone suppresses aldosterone/ salt-induced expression of NOX-4. | |
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MedLine Citation:
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PMID: 21292834 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: Salt-induced hypertension in the Dahl rat is associated with increases in angiotensin II, aldosterone, free radical generation and endothelial dysfunction. However, little is known about the specific mechanism(s) associated with the end-organ damage effects of aldosterone. We hypothesised that eplerenone reduces kidney damage by blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. METHODS: Dahl salt-sensitive rats fed either a low-salt (LS) or high-salt (HS) diet were treated with aldosterone in the presence of eplerenone or apocynin. Indirect blood pressure was measured prior to start of diet and weekly thereafter. Levels of plasma nitric oxide (NO) and urinary 8-isoprostane were measured following treatment. Protein levels of selected subunits of NADPH were assessed by western blot. RESULTS: Eplerenone and apocynin inhibited the rise in blood pressure induced by HS and/or aldosterone. This observation was accompanied with a parallel change in kidney protein levels of NADPH oxidase 4 (NOX-4) and p22phox. Aldosterone and high salt were associated with lower NO levels and greater renal oxidative stress. CONCLUSIONS: NADPH oxidase is associated with the vascular and renal remodelling observed in high dietary salt intake. Aldosterone-induced expression of NOX-4 plays a pivotal role in the end-organ damage effect of aldosterone, as eplerenone tended to reduce kidney damage and inhibit NOX expression. |
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Authors:
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Mohamed A Bayorh; Aisha Rollins-Hairston; Jeffery Adiyiah; Deborah Lyn; Danita Eatman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-02-03 |
Journal Detail:
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Title: Journal of the renin-angiotensin-aldosterone system : JRAAS Volume: 12 ISSN: 1752-8976 ISO Abbreviation: J Renin Angiotensin Aldosterone Syst Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-01 Completed Date: 2011-12-27 Revised Date: 2012-05-16 |
Medline Journal Info:
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Nlm Unique ID: 100971636 Medline TA: J Renin Angiotensin Aldosterone Syst Country: England |
Other Details:
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Languages: eng Pagination: 195-201 Citation Subset: IM |
Affiliation:
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Morehouse School of Medicine, GA 30310-1495, USA. bayorh@msm.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetophenones
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pharmacology Aldosterone / pharmacology* Animals Blood Pressure / drug effects Blotting, Western Body Weight / drug effects Dinoprost / analogs & derivatives, urine Male NADPH Oxidase / metabolism* Nitric Oxide / blood Protein Subunits / metabolism Proteinuria / blood, pathology Rats Rats, Inbred Dahl Sodium / urine Sodium Chloride, Dietary / pharmacology* Spironolactone / analogs & derivatives*, pharmacology Systole / drug effects Urinalysis |
| Grant Support | |
ID/Acronym/Agency:
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1SC1DK082385-01/DK/NIDDK NIH HHS; G12-RR03034/RR/NCRR NIH HHS; SC1 DK082385/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Acetophenones; 0/Protein Subunits; 0/Sodium Chloride, Dietary; 0/eplerenone; 10102-43-9/Nitric Oxide; 27415-26-5/8-epi-prostaglandin F2alpha; 498-02-2/acetovanillone; 52-01-7/Spironolactone; 52-39-1/Aldosterone; 551-11-1/Dinoprost; 7440-23-5/Sodium; EC 1.6.-/Nox4 protein, rat; EC 1.6.3.1/NADPH Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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