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 17beta-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 17beta-estradiol decreased superoxide production (P<0.05). NADPH-induced relaxations of BA were smaller in 17beta-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.
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 17beta-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 17beta-estradiol decreased superoxide production (P<0.05). NADPH-induced relaxations of BA were smaller in 17beta-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.
Authors: João D Mattos; Monique O Campos; Marcos P Rocha; Daniel E Mansur; Helena N M Rocha; Vinicius P Garcia; Gabriel Batista; Thiago S Alvares; Gustavo V Oliveira; Mônica V Souza; Rogério L R Videira; Natalia G Rocha; Niels H Secher; Antonio C L Nóbrega; Igor A Fernandes Journal: J Physiol Date: 2018-12-26 Impact factor: 5.182
Authors: David W Howells; Michelle J Porritt; Sarah S J Rewell; Victoria O'Collins; Emily S Sena; H Bart van der Worp; Richard J Traystman; Malcolm R Macleod Journal: J Cereb Blood Flow Metab Date: 2010-05-19 Impact factor: 6.200
Authors: Pamela W M Kleikers; K Wingler; J J R Hermans; I Diebold; S Altenhöfer; K A Radermacher; B Janssen; A Görlach; H H H W Schmidt Journal: J Mol Med (Berl) Date: 2012-10-23 Impact factor: 4.599
Authors: Arnaldo Lopez-Ruiz; Julio Sartori-Valinotti; Licy L Yanes; Radu Iliescu; Jane F Reckelhoff Journal: Am J Physiol Heart Circ Physiol Date: 2008-06-20 Impact factor: 4.733