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The present study aimed to investigate the cellular mechanisms responsible for the therapeutic benefits of rosuvastatin in ameliorating diabetes\u2010associated endothelial dysfunction.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> Twelve\u2010week\u2010old <jats:italic>db\/db<\/jats:italic> diabetic mice were treated with rosuvastatin at 20\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> p.o.for 6 weeks. Isometric force was measured in isolated aortae and renal arteries. Protein expressions including angiotensin II type 1 receptor (AT<jats:sub>1<\/jats:sub>R), NOX4, p22<jats:sup>phox<\/jats:sup>, p67<jats:sup>phox<\/jats:sup>, Rac\u20101, nitrotyrosine, phospho\u2010ERK1\/2 and phospho\u2010p38 were determined by Western blotting, while reactive oxygen species (ROS) accumulation in the vascular wall was evaluated by dihydroethidium fluorescence and lucigenin assay.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Rosuvastatin treatment of <jats:italic>db\/db<\/jats:italic> mice reversed the impaired ACh\u2010induced endothelium\u2010dependent dilatations in both renal arteries and aortae and prevented the exaggerated contractions to angiotensin II and phenylephrine in <jats:italic>db\/db<\/jats:italic> mouse renal arteries and aortae. Rosuvastatin reduced the elevated expressions of AT<jats:sub>1<\/jats:sub>R, p22<jats:sup>phox<\/jats:sup> and p67<jats:sup>phox<\/jats:sup>, NOX4, Rac1, nitrotyrosine and phosphorylation of ERK1\/2 and p38 MAPK and inhibited ROS production in aortae from <jats:italic>db\/db<\/jats:italic> mice.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> The vasoprotective effects of rosuvastatin are attributed to an increase in NO bioavailability, which is probably achieved by its inhibition of ROS production from the AT<jats:sub>1<\/jats:sub>R\u2010NAD(P)H oxidase cascade.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01416.x","type":"journal-article","created":{"date-parts":[[2011,4,12]],"date-time":"2011-04-12T10:28:55Z","timestamp":1302604135000},"page":"598-606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Rosuvastatin improves endothelial function in <i>db\/db<\/i> mice: role of angiotensin II 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