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Further, the cardiovascular pathology pre-dates neurological decline, however the mechanisms involved remain unclear. We investigated in the R6\/2 mouse model of HD nitric oxide (NO) dependent and independent endothelial mechanisms. Femoral artery reactivity was determined by wire myography in wild type (WT) and R6\/2 mice at 12 and 16 weeks of adulthood. WT mice showed increased endothelial relaxation between 12 and 16 weeks (R<jats:sub>max<\/jats:sub>: 72\u2009\u00b1\u20097% <jats:italic>vs<\/jats:italic>. 97\u2009\u00b1\u200913%, P\u2009&lt;\u20090.05). In contrast, R6\/2 mice showed enhanced endothelial relaxation already by 12 weeks (R<jats:sub>max<\/jats:sub> at 12w: 72\u2009\u00b1\u20097% <jats:italic>vs<\/jats:italic>. 94\u2009\u00b1\u20095%, WT <jats:italic>vs<\/jats:italic>. R6\/2, P\u2009&lt;\u20090.05) that declined by 16 weeks compared with WT mice (R<jats:sub>max<\/jats:sub> at 16w: 97\u2009\u00b1\u200913% <jats:italic>vs<\/jats:italic>. 68\u2009\u00b1\u20097%, WT <jats:italic>vs<\/jats:italic>. R6\/2, P\u2009&lt;\u20090.05). In WT mice, the increase in femoral relaxation between 12 and 16 weeks was due to enhanced NO dependent mechanisms. By 16 weeks of adult age, the R6\/2 mouse developed overt endothelial dysfunction due to an inability to increase NO dependent vasodilation. The data add to the growing literature of non-neural manifestations of HD and implicate NO depletion as a key mechanism underlying the HD pathophysiology in the peripheral vasculature.<\/jats:p>","DOI":"10.1038\/srep25979","type":"journal-article","created":{"date-parts":[[2016,5,16]],"date-time":"2016-05-16T09:42:17Z","timestamp":1463391737000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impaired Nitric Oxide Mediated Vasodilation In The Peripheral Circulation In The R6\/2 Mouse Model Of Huntington\u2019s Disease"],"prefix":"10.1038","volume":"6","author":[{"given":"Andrew D.","family":"Kane","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youguo","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio A.","family":"Herrera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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