Effect of gender on NADPH-oxidase activity, expression, and function in the cerebral circulation: role of estrogen

Miller, A. A. , Drummond, G. R., Mast, A. E., Schmidt, H. H.H.W. and Sobey, C. G. (2007) Effect of gender on NADPH-oxidase activity, expression, and function in the cerebral circulation: role of estrogen. Stroke, 38(7), pp. 2142-2149. (doi: 10.1161/STROKEAHA.106.477406) (PMID:17525399)

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Background and Purpose— This study tested whether NADPH-oxidase activity, expression, and functional effects on vascular tone are influenced by gender in the rat cerebral circulation and whether such differences are estrogen-dependent. Methods— NADPH-stimulated superoxide production by cerebral (basilar [BA]; middle cerebral) arteries from male and female Sprague-Dawley rats was measured using lucigenin-enhanced chemiluminescence and dihydroethidium. Protein expression of Nox1, Nox2, Nox4, superoxide dismutase 1 (SOD1), SOD2, and SOD3 was measured using Western blotting. Vascular responses of BA to NADPH were assessed in a myograph. Some female rats were ovariectomized and treated with either vehicle (dimethyl sulfoxide) or 17β-estradiol. Results— NADPH-stimulated superoxide production by BA and middle cerebral arteries from males was approximately 2-fold greater than vessels from females. Superoxide production was virtually abolished by the NADPH-oxidase inhibitor, diphenyleneiodonium. Protein expression of Nox1 and Nox4 in BA was also higher in males than in females (2.4- and 2.8-fold, respectively), whereas Nox2, SOD1, SOD2, and SOD3 expression did not differ between genders. NADPH induced greater vasorelaxant effects in BA from males versus females (P<0.05). The hydrogen peroxide scavenger, catalase, abolished these NADPH-induced relaxations. NADPH-stimulated superoxide production by BA from ovariectomized rats treated with vehicle was 3-fold greater than levels in intact females. Treatment of ovariectomized rats with 17β-estradiol decreased superoxide production (P<0.05). NADPH-induced relaxations of BA were smaller in 17β-estradiol-treated than in vehicle-treated ovariectomized rats (P<0.05). Conclusions— NADPH-oxidase activity and function are lower in cerebral arteries of female rats. These gender differences are estrogen-dependent and are associated with lower Nox1 and Nox4 expression.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Miller, Dr Alyson
Authors: Miller, A. A., Drummond, G. R., Mast, A. E., Schmidt, H. H.H.W., and Sobey, C. G.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Stroke
Publisher:American Heart Association
ISSN (Online):1524-4628

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