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Modulation of cerebral vascular tone by NADPH oxidase
Author(s) -
Miller Alyson,
Paravicini Tamara,
Drummond Grant,
Sobey Christopher
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a725-b
Subject(s) - apocynin , nadph oxidase , superoxide , chemistry , cerebral arteries , nox1 , medicine , nox4 , endocrinology , angiotensin ii , catalase , mesenteric arteries , superoxide dismutase , reactive oxygen species , oxidative stress , biochemistry , artery , enzyme , receptor
The aims of this study were to compare the activity and function of NADPH oxidase in rat intracranial cerebral (including basilar, BA) and systemic (including carotid artery, CA; mesenteric artery, MA; and aorta, AO) arteries, and to investigate potential physiological roles for NADPH oxidase in cerebral arteries. NADPH oxidase‐derived superoxide was measured using lucigenin‐enhanced chemiluminescence and dihydroethidium. The effect of NADPH oxidase activation on vascular tone was investigated in vitro and in vivo . NADPH‐ and angiotensin II‐stimulated superoxide production was up to 100‐fold greater in cerebral versus systemic arteries. The NADPH oxidase inhibitors, diphenyleneiodonium (DPI), gp91ds‐tat, and apocynin attenuated superoxide production. This was associated with 10‐fold greater expression of Nox4 protein in the BA versus AO, CA and MA. In vitro , NADPH relaxed arteries with the efficacy: BA>MA>AO=CA. Catalase or apocynin inhibited NADPH‐induced relaxation. Contraction to angiotensin II was weaker in BA versus AO and CA, but was selectively potentiated by catalase and apocynin. In vivo , flow‐dependent dilatation of the BA was associated with an increase in superoxide production in BA endothelial cells. Catalase and DPI inhibited flow‐dependent dilatation. Thus, NADPH oxidase activity and function is profoundly higher in cerebral versus systemic arteries. In the BA, H 2 O 2 generated from NADPH oxidase–derived superoxide offsets Ang II‐induced contraction and partially mediates flow‐dependent dilatation. These findings provide evidence supporting a physiological role for NADPH oxidase in modulating cerebral vascular tone.