Document Detail


Involvement of oxidative stress in the profibrotic action of aldosterone. Interaction wtih the renin-angiotension system.
MedLine Citation:
PMID:  15243979     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The aim of this study was to investigate the involvement of angiotensin II and oxidative stress on cardiovascular damage induced by chronic subcutaneous aldosterone infusion in the absence of salt loading. METHODS: Sprague-Dawley rats were infused with d-aldosterone (0.75 microg/h subcutaneously) for 6 weeks. Blood pressure was measured with the tail-cuff method. Small arteries were investigated on a pressurized myograph. Cardiovascular and renal collagen was evaluated by Sirius red staining. Systemic oxidant excess was measured with plasma 8-isoprostane by ELISA and by measurement of thiobarbituric acid-reactive substances. Vascular reactive oxygen species were studied using hydroethidine and NADPH-generated superoxide anion measured by lucigenin chemiluminescence. RESULTS: After 6 weeks of treatment, systolic blood pressure was significantly increased in aldosterone-infused rats (170+/-8 v 123+/-2 mm Hg in controls, P < .05). Progression of hypertension was partially prevented by co-administration of losartan (AT1 receptor blocker) or tempol (superoxide dismutase mimetic): 140+/-4 and 149+/-6 mm Hg, respectively, P < .05 versus the aldosterone group. Aldosterone induced renal but not cardiac hypertrophy, which was not prevented by losartan or by tempol. Moreover, losartan and tempol failed to prevent vascular hypertrophy of resistance mesenteric vessels. However, losartan (0.77%+/-0.05%) and tempol (0.65%+/-0.10%) prevented cardiac fibrosis in the midmyocardium in the aldosterone group (1.03%+/-0.12% v 0.68%+/-0.07% positive staining per area in control, P < .05). In the kidney, collagen accumulation of aldosterone-infused rats was also significantly decreased by losartan (-77%) and tempol (-60%). Similar effects were obtained on aortic fibrosis. Aldosterone increased serum 8-isoprostane levels.This increase was blunted by losartan and tempol. Losartan and tempol totally prevented vascular, cardiac, and renal increase of NADPH-induced superoxide production stimulated by aldosterone. CONCLUSIONS: Our data suggest that the profibrotic but not the hypertrophic action of aldosterone are mediated at least in part by reactive oxygen species generation and involve an interaction with the renin-angiotensin system.
Authors:
Marc Iglarz; Rhian M Touyz; Emilie C Viel; Farhad Amiri; Ernesto L Schiffrin
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of hypertension     Volume:  17     ISSN:  0895-7061     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-09     Completed Date:  2004-11-06     Revised Date:  2009-02-24    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  597-603     Citation Subset:  IM    
Affiliation:
Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Aldosterone / administration & dosage*
Animals
Antihypertensive Agents / administration & dosage
Antioxidants / administration & dosage
Biological Markers / blood
Blood Pressure / drug effects
Cyclic N-Oxides / administration & dosage
Disease Models, Animal
Endocardium / drug effects,  pathology
Endothelium, Vascular / drug effects,  metabolism,  physiopathology
Fibrosis
Infusions, Intra-Arterial
Kidney / drug effects,  pathology
Losartan / administration & dosage
Male
Models, Cardiovascular
NADP / drug effects,  metabolism
Nitroprusside / administration & dosage
Oxidative Stress / drug effects*
Pericardium / drug effects,  pathology
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Renin-Angiotensin System / drug effects*
Spin Labels
Systole / drug effects
Thiobarbituric Acid Reactive Substances / metabolism
Vasodilator Agents / administration & dosage
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Antioxidants; 0/Biological Markers; 0/Cyclic N-Oxides; 0/Reactive Oxygen Species; 0/Spin Labels; 0/Thiobarbituric Acid Reactive Substances; 0/Vasodilator Agents; 114798-26-4/Losartan; 15078-28-1/Nitroprusside; 2226-96-2/tempol; 52-39-1/Aldosterone; 53-59-8/NADP
Comments/Corrections
Comment In:
Am J Hypertens. 2005 Mar;18(3):441   [PMID:  15797667 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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