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Blood pressure has only minor influence on aldosterone-induced oxidative stress and DNA damage in vivo.
MedLine Citation:
PMID:  23104102     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Epidemiological studies found an increased kidney cancer risk in hypertensive patients. These patients frequently present an increase of the mineralocorticoid aldosterone (Ald) due to a stimulated renin angiotensin aldosterone system (RAAS). Recently, we showed prooxidative and genotoxic effects of Ald in vitro. Here, we investigated the influence of blood pressure on aldosterone-induced oxidative damage. To distinguish whether effects in Sprague-Dawley rats treated with Ald were caused by Ald or by increased blood pressure, the mineralocorticoid receptor (MR) antagonist spironolactone was administered in a subtherapeutical dose, not lowering the blood pressure, while hydralazine, a RAAS-independent vasodilator, was given to normalize the pressure. With the antioxidant tempol, oxidative stress-dependent effects were demonstrated. Ald treatment caused kidney damage, oxidative and nitrative stress. Structural DNA damage and the mutagenic oxidative base modification 7,8-dihydro-8-oxo-guanine were increased, as well as DNA repair activity and nuclear NF-κB translocation. Spironolactone and tempol decreased all markers significantly, while hydralazine had just slight effects. These data comprise the first report of essentially blood pressure-independent tissue- and DNA-damaging effects of Ald. A fully activated MR and the production of reactive oxygen and nitrogen species were crucial for these effects.
Authors:
Nina Queisser; Kerstin Amann; Valentin Hey; Samy L Habib; Nicole Schupp
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-23
Journal Detail:
Title:  Free radical biology & medicine     Volume:  -     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
Institute of Pharmacology and Toxicology, University of Würzburg, Germany.
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