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• W2111903934 abstract "Background and Purpose— We tested the hypothesis that elevated superoxide production by Nox2-NADPH oxidase occurs in cerebral arteries during hypercholesterolemia and causes decreased nitric oxide function. Methods— Wild-type (WT), apolipoprotein E-deficient (ApoE −/− ) and Nox2 −/− /ApoE −/− mice were fed a high-fat diet for 7 to 14 weeks. Basal superoxide production by cerebral arteries was measured using L-012 (100 μmol/L)-enhanced chemiluminescence. Nitric oxide function was assessed in isolated middle cerebral arteries through the constrictor response to N ω -nitro- l -arginine methyl ester ( l -NAME; 100 μmol/L). Western blotting was used to measure protein expression of Nox2, p47phox, endothelial nitric oxide synthase, and superoxide dismutases (1–3). Results— Morphology of cerebral arteries was similar in WT and ApoE −/− mice. In ApoE −/− , but not Nox2 −/− /ApoE −/− mice, superoxide production by cerebral arteries was approximately 50% greater than in WT mice ( P <0.05). Moreover, the magnitude of l -NAME-induced contractions of isolated middle cerebral arteries from ApoE −/− mice was <50% of that in WT mice ( P <0.05), whereas in Nox2 −/− /ApoE −/− mice, the contractile response was comparable to WT responses. In the presence of the superoxide scavenger, tempol (1 mmol/L), l -NAME-induced contractions of middle cerebral arteries were similar between WT and ApoE −/− mice. Expression of p47phox was approximately 2-fold higher in ApoE −/− versus WT mice, whereas Nox2, endothelial nitric oxide synthase, and superoxide dismutase isoforms were unchanged. Conclusions— Elevated superoxide production and reduced basal nitric oxide-mediated relaxation occur in cerebral arteries of hypercholesterolemic mice even in the absence of lesions. These changes appear to be exclusively due to increased activity of Nox2-NADPH oxidase, possibly through increased expression of its regulatory subunit p47phox." @default.
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• W2111903934 date "2010-04-01" @default.
• W2111903934 modified "2023-10-03" @default.
• W2111903934 title "Augmented Superoxide Production By Nox2-Containing NADPH Oxidase Causes Cerebral Artery Dysfunction During Hypercholesterolemia" @default.
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• W2111903934 doi "https://doi.org/10.1161/strokeaha.109.575365" @default.
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