| Increased oxidative stress, the renin-angiotensin system, and sympathetic overactivation induce hypertension in kidney androgen-regulated protein transgenic mice. | |
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MedLine Citation:
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PMID: 21906672 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Gender differences in the incidence and severity of hypertension have suggested the involvement of a sex-dependent mechanism. Transgenic (Tg) mice overexpressing kidney androgen-regulated protein (KAP) specifically in kidney showed hypertension associated with oxidative stress. Reactive oxygen species (ROS) are strongly implicated in the pathological signaling leading to hypertension in a framework that includes renin-angiotensin system (RAS) activation, increased sympathetic activity, and cardiac remodeling. In this report, we observed that plasma levels of angiotensin II and catecholamines were increased in KAP Tg mice, compared with wild-type animals. Systemic administration of Tempol, a membrane-permeative superoxide dismutase mimetic, reduced arterial pressure as well as urinary excretion of oxidative stress markers and reduced both angiotensin II and norepinephrine plasma levels in KAP Tg mice. Intracerebroventricular administration of Tempol also reduced arterial pressure in Tg mice. Moreover, administration of apocynin and DPI, inhibitors of NADPH oxidase, a major source of ROS, also reduced arterial pressure and both angiotensin II and norepinephrine plasma levels in Tg mice. Thus, we analyzed the involvement of the RAS and sympathetic nervous system in KAP Tg mouse hypertension. Both captopril and losartan reduced arterial blood pressure in Tg mice, as also occurred after β-adrenergic blockade with atenolol. Also, intracerebroventricular losartan administration reduced arterial pressure in KAP Tg mice. Our data demonstrate that hypertension in male KAP Tg mice is based on increased oxidative stress, increased sympathetic activity, and RAS activation. Moreover, our results suggest a role for increased oxidative stress in the CNS as a major cause of hypertension in these animals. |
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Authors:
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María T Grande; Gloria Pascual; Adela S Riolobos; Milagros Clemente-Lorenzo; Beatriz Bardaji; Luz Barreiro; Olga Tornavaca; Anna Meseguer; Jose M López-Novoa |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-25 |
Journal Detail:
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Title: Free radical biology & medicine Volume: - ISSN: 1873-4596 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-9-12 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 © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Renal and Cardiovascular Physiopathology Unit, Departamento de Fisiología y Farmacología, Instituto de Neurociencias de Castilla y León, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto Reina Sofía de Investigación Nefrológica, Fundación Renal Iñigo Alvarez de Toledo, Spain. |
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