Increased NADPH oxidase activity mediates spontaneous aortic tone in genetically hypertensive rats

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• 作者：Federica Lodi ; Angel Cogolludo ; Juan Duarte ; Laura Moreno ; Alfredo Coviello ; Maria Peral De Bruno ; Rocio Vera ; Milagros Galisteo ; Rosario Jim&#xe9 ; nez ; Juan Tamargo and Francisco Perez-Vizcaino
• 关键词：p47p>phoxp> ; SHR (spontaneously hypertensive rat) ; Spontaneous tone ; Superoxide
• 刊名：European Journal of Pharmacology
• 出版年：2006
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：21 August 2006
• 卷：544
• 期：1-3
• 页码：97-103
• 文件大小：258 K

摘要

NADPH oxidase is critically involved in increased blood pressure, vascular hypertrophy, inflammation and endothelial dysfunction in experimental and clinical hypertension. We hypothesized that NADPH oxidase might also play a role in the development of spontaneous aortic tone in spontaneously hypertensive rats (SHR). Wistar Kyoto rats (WKY) were used as normotensive controls. Tone was recorded under isometric conditions. NADPH oxidase activity was measured by both lucigenin luminescence and dihydroethidium fluorescence. p47p>phoxp> protein was localized by immunohistochemistry. SHR (but not WKY rat) aortae showed spontaneous tone in the absence of exogenous vasoconstrictors as evidenced by a stronger relaxant effect of Cap>2+p>-free sodium nitroprusside solution. This tone was enhanced in endothelium-denuded arteries and was inhibited by superoxide dismutase, apocynin, diphenylene iodonium and quercetin. Aortic NADPH oxidase activity, measured by both lucigenin luminescence and dihydroethidium fluorescence, was increased in SHR compared with WKY rats. Immunohistochemical analysis revealed a strong increase in p47p>phoxp> expression in the medial layer in SHR. Taken together, the present results indicate that enhanced NADPH oxidase activity and, hence, NADPH driven O₂p>−p> production, is involved in the spontaneous aortic tone in SHR. This was associated with an increased expression of p47p>phoxp> in the medial layer of the aorta.