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We have previously demonstrated that acute treatment with the newly discovered organic nitrate, 2\u2010nitrate\u20101,3\u2010dibuthoxypropan (NDBP), is associated with NO\u2010like effects in the vasculature. This study aimed to further characterize the mechanism(s) and to elucidate the therapeutic potential in a model of hypertension and oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>A combination of <jats:italic>ex vivo<\/jats:italic>, <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> approaches was used to assess the effects of NDBP on vascular reactivity, NO release, NADPH oxidase activity and in a model of hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:italic>Ex vivo<\/jats:italic> vascular studies demonstrated NDBP\u2010mediated vasorelaxation in mesenteric resistance arteries, which was devoid of tolerance. <jats:italic>In vitro<\/jats:italic> studies using liver and kidney homogenates revealed dose\u2010dependent and sustained NO generation by NDBP, which was attenuated by the xanthine oxidase inhibitor febuxostat. In addition, NDBP reduced NADPH oxidase activity in the liver and prevented angiotensin II\u2010induced activation of NADPH oxidase in the kidney. <jats:italic>In vivo<\/jats:italic> studies showed that NDBP halted the progression of hypertension in mice with chronic angiotensin II infusion. This was associated with attenuated cardiac hypertrophy, and reduced NADPH oxidase\u2010derived oxidative stress and fibrosis in the kidney and heart.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The novel organic nitrate NDBP halts the progression of angiotensin II\u2010mediated hypertension. Mechanistically, our findings suggest that NDBP treatment is associated with sustained NO release and attenuated activity of NADPH oxidase, which to some extent requires functional xanthine oxidase.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13511","type":"journal-article","created":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T11:12:45Z","timestamp":1462878765000},"page":"2290-2302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Nitric oxide generation by the organic nitrate NDBP attenuates oxidative stress and angiotensin II\u2010mediated hypertension"],"prefix":"10.1111","volume":"173","author":[{"given":"Su\u00eania K P","family":"Porpino","sequence":"first","affiliation":[{"name":"Dept. of Physiology and Pharmacology Karolinska Institutet  Stockholm Sweden"},{"name":"Dept. of Medical Cell Biology Uppsala University  Uppsala Sweden"},{"name":"Biotechnology Center Federal University of Para\u00edba  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