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British Journal of Pharmacology
Article . 2007 . Peer-reviewed
License: Wiley Online Library User Agreement
Data sources: Crossref
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Failure of antioxidants to protect against angiotensin II‐induced aortic rupture in aged apolipoprotein(E)‐deficient mice

Authors: Fan Jiang; Gregory J. Dusting; Gregory T. Jones;

Failure of antioxidants to protect against angiotensin II‐induced aortic rupture in aged apolipoprotein(E)‐deficient mice

Abstract

Background and purpose:Oxidative stress may be involved in the development of abdominal aortic aneurysms (AAAs). Previous studies indicate that antioxidants protect against AAA formation during chronic angiotensin (Ang) II infusion in apolipoprotein E‐deficient (ApoE0) mice. We here examine if these protective effects also occurred in aged ApoE0mice.Experimental approach:Male ApoE0mice (50–60 weeks) were randomly divided into 4 groups: saline, Ang II (1000 ng kg−1 min−1for 4 weeks), Ang II plus antioxidants (0.1% vitamin E in food plus 0.1% vitamin C in drinking water), and Ang II plus losartan (30 mg kg−1 day−1).Key results:Exogenous Ang II increased systolic blood pressure by 40 mmHg and resulted in the formation of pseudoaneurysms (rupture and extramural haematoma) in the abdominal aorta in 50% of animals. True aneurysmal dilatation was rarely observed. Antioxidants decreased systemic oxidative stress (plasma malondialdehyde), but had only minor effects on aortic rupture, relative to the complete prevention by losartan. Immunohistochemistry revealed strong matrix metalloproteinase‐9 (MMP‐9) expression in atherosclerotic plaques and at the sites of rupture. Antioxidants did not affect tumour necrosis factor‐α‐stimulated MMP‐9 release from U937 cells. In addition, antioxidants had little effects on Ang II‐induced renal dysfunction.Conclusions and implications:In contrast to previous findings in younger mice, antioxidants had only minor effects on Ang II‐induced aortic rupture in aged mice. Our results demonstrate that the pathological features of the aneurysmal remodelling induced by Ang II in old ApoE0mice are distinct from those of human AAA.British Journal of Pharmacology(2007)152, 880–890; doi:10.1038/sj.bjp.0707449; published online 10 September 2007

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Keywords

Male, Mice, Knockout, Aging, Angiotensin II, Aortic Rupture, Blotting, Western, Blood Pressure, Kidney, Kidney Function Tests, Immunohistochemistry, Antioxidants, Mice, Oxidative Stress, Proteinuria, Apolipoproteins E, Matrix Metalloproteinase 9, Creatinine, Animals, Humans, Heme Oxygenase-1

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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
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Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
22
Top 10%
Average
Average
bronze