Document Detail

Role of NAD(P)H oxidase on vascular alterations in angiotensin II-infused mice.
MedLine Citation:
PMID:  15076159     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Angiotensin (Ang) II stimulates vascular reactive oxygen species generation via NAD(P)H oxidase activation. We investigated whether vascular NAD(P)H oxidase influences structure and function of resistance arteries from Ang II-infused mice. METHODS: Mice received Ang II alone (400 ng/kg per min, subcutaneously), Ang II + apocynin (NAD(P)H oxidase inhibitor, 2.5 mg/day, in the food), apocynin alone or Ang II + hydralazine (50 mg/kg per day) for 14 days. Systolic blood pressure (SBP) was measured by tail-cuff methodology and function and structure of small mesenteric arteries were studied in pressurized vessels. Vascular collagen type I/III content was evaluated by confocal immunofluorescence microscopy and by immunoblotting. RESULTS: The rise in SBP induced by Ang II (P < 0.001) was prevented by apocynin and hydralazine. Media/lumen ratio increase in Ang II-infused mice (P < 0.01) was prevented by apocynin. Acetylcholine-mediated relaxation, which was impaired in Ang II-infused mice (P < 0.001), was improved by apocynin. Confocal microscopy and immunoblotting demonstrated increased collagen type I/III content in mesenteric arteries from Ang II-infused mice. Apocynin, but not hydralazine, prevented the increase in collagen abundance in Ang II-infused mice. The increase in vascular NAD(P)H oxidase activity by Ang II (P < 0.001) was prevented by apocynin. CONCLUSIONS: The NAD(P)H oxidase inhibitor apocynin reduced blood pressure elevation and prevented structural alterations, endothelial dysfunction, and collagen deposition in the media of small arteries in Ang II-infused mice. Although hydralazine also decreased blood pressure, it had no effects on vascular collagen content. Our findings suggest that NAD(P)H oxidase activity plays an important role in vascular functional and structural changes and in the composition of the vascular wall in Ang II-dependent hypertension.
Agostino Virdis; Mario Fritsch Neves; Farhad Amiri; Rhian M Touyz; Ernesto L Schiffrin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  22     ISSN:  0263-6352     ISO Abbreviation:  J. Hypertens.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-04-12     Completed Date:  2004-10-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  535-42     Citation Subset:  IM    
CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
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MeSH Terms
Acetophenones / pharmacology
Angiotensin II / pharmacology*
Blood Pressure / drug effects,  physiology
Body Weight
Collagen / metabolism
Endothelium, Vascular / metabolism
Enzyme Inhibitors / pharmacology
Hydralazine / pharmacology
Hypertension / metabolism,  physiopathology*
Mesenteric Arteries / physiology
Mice, Inbred BALB C
NADPH Oxidase / antagonists & inhibitors,  metabolism*
Vascular Resistance / drug effects*,  physiology*
Vasoconstrictor Agents / pharmacology*
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/Acetophenones; 0/Enzyme Inhibitors; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 11128-99-7/Angiotensin II; 498-02-2/acetovanillone; 86-54-4/Hydralazine; 9007-34-5/Collagen; EC Oxidase

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

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