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Here, we investigated whether WBS affects aortic structure and function in the complete deletion (CD) mouse model harbouring the most common deletion found in WBS patients. Thoracic aortas from 3\u20134 months-old male CD mice and wild-type littermates were mounted in wire myographs or were processed for histomorphometrical analysis. Nitric oxide synthase (NOS) isoforms and oxidative stress levels were assessed. Ascending aortas from young adult CD mice showed moderate (50%) luminal stenosis, whereas endothelial function and oxidative stress were comparable to wild-type. CD mice showed greater contractions to KCl. However, \u03b11-adrenergic contractions to phenylephrine, but not with a thromboxane analogue, were compromised. Decreased phenylephrine responses were not affected by selective inducible NOS blockade with 1400\u2009W, but were prevented by the non-selective NOS inhibitor L-NAME and the selective neuronal NOS inhibitor SMTC. Consistently, CD mice showed increased neuronal NOS expression in aortas. Overall, aortic stenosis in CD mice coexists with excessive nNOS-derived NO signaling that compromises ascending aorta \u03b11-adrenergic contractions. We suggest that increased neuronal NOS signaling may act as a physiological \u2018brake\u2019 against the detrimental effects of stenosis.<\/jats:p>","DOI":"10.1038\/s41598-020-57803-3","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T11:02:51Z","timestamp":1579604571000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Stenosis coexists with compromised \u03b11-adrenergic contractions in the ascending aorta of a mouse model of Williams-Beuren syndrome"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8128-2641","authenticated-orcid":false,"given":"Francesc","family":"Jim\u00e9nez-Altay\u00f3","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Ortiz-Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00eddia","family":"Puertas-Umbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Dantas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Vila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"D\u2019Ocon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-2041","authenticated-orcid":false,"given":"Victoria","family":"Campuzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,21]]},"reference":[{"key":"57803_CR1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1056\/NEJMra0903074","volume":"362","author":"BR Pober","year":"2010","unstructured":"Pober, B. 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