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The aim of this study was to examine whether resveratrol decreases the generation of reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>), thereby reducing BP in rats with fructose\u2010induced hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Rats were fed 10% fructose with or without resveratrol (10\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) for 1 week or for 4 weeks with resveratrol treatment beginning at week 2; systolic BP (<jats:styled-content style=\"fixed-case\">SBP<\/jats:styled-content>) was measured by tail\u2010cuff method. Endogenous <jats:italic>in vivo<\/jats:italic> O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> production in the nucleus tractus solitarii (<jats:styled-content style=\"fixed-case\">NTS<\/jats:styled-content>) was determined with dihydroethidium. Real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and immunoblotting analyses were used to quantify <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and protein expression levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">In fructose\u2010fed rats, ROS<\/jats:styled-content> levels in the <jats:styled-content style=\"fixed-case\">NTS<\/jats:styled-content> were higher, whereas the <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> level was significantly decreased. Also, <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and protein levels of <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> oxidase subunits (p67, p22\u2010phox) were elevated, superoxide dismutase 2 (SOD2) reduced and AMP\u2010activated PK (<jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>) <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>172 phosphorylation levels in the <jats:styled-content style=\"fixed-case\">NTS<\/jats:styled-content> were lower in fructose\u2010fed rats. Treatment with the <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> activator resveratrol decreased levels of <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> oxidase subunits and ROS, and increased NO and SOD2 levels in the NTS of fructose\u2010fed rats. Administration of resveratrol, in combination with fructose at week 0 and later at week 2, significantly reduced the SBP of fructose\u2010fed rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Collectively, resveratrol decreased <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> through the phosphorylation of <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">Akt<\/jats:styled-content> and neuronal <jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content> in fructose\u2010fed rats. These novel findings suggest that resveratrol may be a potential pharmacological candidate for the treatment of hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12648","type":"journal-article","created":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T12:09:03Z","timestamp":1392725343000},"page":"2739-2750","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Resveratrol decreases fructose\u2010induced oxidative stress, mediated by <scp>NADPH<\/scp> oxidase via an <scp>AMPK<\/scp>\u2010dependent mechanism"],"prefix":"10.1111","volume":"171","author":[{"given":"Pei\u2010Wen","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Medical Education and Research Kaohsiung Veterans General Hospital  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Yu","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine 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