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Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and <jats:italic>Nos3<\/jats:italic> promoter DNA methylation in arteries from eight\u2010month\u2010old guinea\u2010pig born from control, FGR\u2010treated and FGR\u2010NAC\u2010treated pregnancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Femoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site\u2010specific DNA methylation in <jats:italic>Nos3<\/jats:italic> promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FGR adult showed an increased femoral vascular resistance (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05), stiffness (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05) and arterial remodelling (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.01), along with an impaired NO\u2010mediated relaxation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001). These effects were prevented by maternal treatment with NAC. Endothelial\u2010NOS mRNA levels were decreased in FGR adult compared with control and FGR\u2010NAC (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05), associated with increased DNA methylation levels (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.01). Comparison of <jats:italic>Nos3<\/jats:italic> DNA methylation in AEC showed a differential methylation pattern between foetal and adult guinea\u2010pigs (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Altogether, these data suggest that adult vascular dysfunction in the FGR does not result from early changes in <jats:italic>Nos3<\/jats:italic> promoter DNA methylation, but from an altered vessel structure established during foetal development.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13328","type":"journal-article","created":{"date-parts":[[2019,6,9]],"date-time":"2019-06-09T06:23:37Z","timestamp":1560061417000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Adult vascular dysfunction in foetal growth\u2010restricted guinea\u2010pigs is associated with a neonate\u2010adult switching in <i>Nos3<\/i> DNA methylation"],"prefix":"10.1111","volume":"227","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3563-6143","authenticated-orcid":false,"given":"Bernardo J.","family":"Krause","sequence":"first","affiliation":[{"name":"Departament of Neonatology, Division of Paediatrics, Faculty of Medicine Pontificia Universidad Cat\u00f3lica de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Pe\u00f1aloza","sequence":"additional","affiliation":[{"name":"Departament of Neonatology, Division of Paediatrics, Faculty of Medicine Pontificia Universidad Cat\u00f3lica de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Candia","sequence":"additional","affiliation":[{"name":"Programa de Fisiopatolog\u00eda, Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina Universidad de Chile Santiago 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Jos\u00e9","family":"Peralta\u2010Scholz","sequence":"additional","affiliation":[{"name":"Departament of Neonatology, Division of Paediatrics, Faculty of Medicine Pontificia Universidad Cat\u00f3lica de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Qu\u00edmicas y Biol\u00f3gicas, Facultad de Salud Universidad Bernardo O'Higgins Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Garc\u00eda\u2010Herrera","sequence":"additional","affiliation":[{"name":"Departamento de Ingenier\u00eda Mec\u00e1nica, Facultad de Ingenier\u00eda Universidad de Santiago de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio A.","family":"Herrera","sequence":"additional","affiliation":[{"name":"Programa de Fisiopatolog\u00eda, Instituto de Ciencias Biom\u00e9dicas, Facultad de 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