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Gender influences cerebral vascular responses to angiotensin II through Nox2‐derived reactive oxygen species
Author(s) -
De Silva Travice Michael,
Broughton Brad,
Drummond Grant,
Sobey Christopher,
Miller Alyson
Publication year - 2009
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.23.1_supplement.935.4
Subject(s) - medicine , endocrinology , nadph oxidase , nox4 , enos , reactive oxygen species , myograph , angiotensin ii , superoxide , chemistry , cerebral arteries , nitric oxide synthase , oxidative stress , renin–angiotensin system , superoxide dismutase , nitric oxide , receptor , enzyme , biochemistry , blood pressure
This study tested whether gender influences cerebrovascular responses to angiotensin II (AngII) and the role(s) of Nox2‐containing NADPH oxidase. AngII (0.1 μmol/L)‐stimulated superoxide (O 2 − ) production by cerebral arteries from male and female C57Bl6/J (WT) and Nox2 −/− mice was measured using lucigenin (5 μM)‐ and L‐012 (100 μM)‐ enhanced chemiluminescence. Hydrogen peroxide (H 2 O 2 ) production was measured by Amplex Red fluorescence. Contractile responses of middle cerebral arteries (MCA) to AngII (0.1‐1 μM) were measured in a perfusion myograph. Protein expression of Nox2, O 2 − dismutases (SOD1‐3), angiotensin receptors (AT 1 , AT 2 ) and endothelial nitric oxide synthase (eNOS) was measured by Western Blotting. Immunofluorescence was used to localize Nox2. AngII‐stimulated O 2 − and H 2 O 2 production by cerebral arteries from female WT mice was ~75% lower vs. males (n=7; P <0.05). AngII elicited smaller contractions of MCA from female WT mice vs. males (n=6; P <0.05). ROS production and contractions were markedly reduced in male, but not female, Nox2 −/− mice (n=6; P <0.05). Expression of Nox2, SOD, AT 1 , AT 2 and eNOS were similar between genders (n=5‐14). In both genders, Nox2 was localized to adventitial and endothelial cells of MCA. Thus, the female gender is associated with lower cerebrovascular ROS production and smaller contractions to AngII. These gender differences are dependent on Nox2. NHMRC (491133).