title: Role of Nox isoforms in angiotensin II-induced oxidative stress and endothelial dysfunction in brain.
abstract: Angiotensin II (Ang II) promotes vascular disease through several mechanisms including by producing oxidative stress and endothelial dysfunction. Although multiple potential sources of reactive oxygen species exist, the relative importance of each is unclear, particularly in individual vascular beds. In these experiments, we examined the role of NADPH oxidase (Nox1 and Nox2) in Ang II-induced endothelial dysfunction in the cerebral circulation. Treatment with Ang II (1.4 mg·kg(-1)·day(-1) for 7 days), but not vehicle, increased blood pressure in all groups. In wild-type (WT; C57Bl/6) mice, Ang II reduced dilation of the basilar artery to the endothelium-dependent agonist acetylcholine compared with vehicle but had no effect on responses in Nox2-deficient (Nox2(-/y)) mice. Ang II impaired responses to acetylcholine in Nox1 WT (Nox1(+/y)) and caused a small reduction in responses to acetylcholine in Nox1-deficient (Nox1(-/y)) mice. Ang II did not impair responses to the endothelium-independent agonists nitroprusside or papaverine in either group. In WT mice, Ang II increased basal and phorbol-dibutyrate-stimulated superoxide production in the cerebrovasculature, and these increases were abolished in Nox2(-/y) mice. Overall, these data suggest that Nox2 plays a relatively prominent role in mediating Ang II-induced oxidative stress and cerebral endothelial dysfunction, with a minor role for Nox1.
authors.affiliation: Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Sophocles
authors.initials: S
authors.lastname: Chrissobolis
authors.forename: Botond
authors.initials: B
authors.lastname: Banfi
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
authors.forename: Frank M
authors.initials: FM
authors.lastname: Faraci
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D009247:NADH, NADPH Oxidoreductases; C488842:Cybb protein, mouse; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C000614711:NOX1 protein, mouse