| Blood pressure has only minor influence on aldosterone-induced oxidative stress and DNA damage in vivo. | |
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MedLine Citation:
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PMID: 23104102 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Nina Queisser; Kerstin Amann; Valentin Hey; Samy L Habib; Nicole Schupp |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-23 |
Journal Detail:
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Title: Free radical biology & medicine Volume: - ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Inc. |
Affiliation:
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Institute of Pharmacology and Toxicology, University of Würzburg, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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