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Loss of eNOS function is associated with increased susceptibility to atherosclerosis, hypertension, thrombosis and stroke. Aortopathy and cardiac hypertrophy have also been found in eNOS null mice, but their aetiology is unclear. We evaluated eNOS nulls before and around birth for cardiac defects, revealing severe abnormalities in the ventricular myocardium and pharyngeal arch arteries. Moreover, in the aortic arch, there were fewer baroreceptors, which sense changes in blood pressure. Adult eNOS null survivors showed evidence of cardiac hypertrophy, aortopathy and cartilaginous metaplasia in the periductal region of the aortic arch. Notch1 and neuregulin were dysregulated in the forming pharyngeal arch arteries and ventricles, suggesting that these pathways may be relevant to the defects observed. Dysregulation of eNOS leads to embryonic and perinatal death, suggesting mutations in eNOS are candidates for causing congenital heart defects in humans. Surviving eNOS mutants have a deficiency of baroreceptors that likely contributes to high blood pressure and may have relevance to human patients who suffer from hypertension associated with aortic arch abnormalities.<\/jats:p>","DOI":"10.1242\/dmm.050265","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T08:45:51Z","timestamp":1702975551000},"source":"Crossref","is-referenced-by-count":3,"title":["eNOS plays essential roles in the developing heart and aorta linked to disruption of Notch signalling"],"prefix":"10.1242","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8094-2254","authenticated-orcid":false,"given":"Lorraine","family":"Eley","sequence":"first","affiliation":[{"name":"Bioscience Institute, Newcastle University, Centre for Life, Central Parkway , Newcastle upon Tyne, NE1 3BZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0666-7036","authenticated-orcid":false,"given":"Rachel V.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Bioscience Institute, Newcastle University, Centre for Life, Central Parkway , Newcastle upon Tyne, NE1 3BZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1145-8474","authenticated-orcid":false,"given":"Ahlam","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Bioscience Institute, Newcastle University, Centre for Life, Central Parkway , Newcastle upon Tyne, NE1 3BZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2833-8882","authenticated-orcid":false,"given":"Bill","family":"Chaudhry","sequence":"additional","affiliation":[{"name":"Bioscience Institute, Newcastle University, Centre for Life, Central Parkway , Newcastle upon Tyne, NE1 3BZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2705-5998","authenticated-orcid":false,"given":"Deborah J.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Bioscience Institute, Newcastle University, Centre for Life, Central Parkway , Newcastle upon Tyne, NE1 3BZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"2024020508380782700_DMM050265C1","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1007\/s00424-010-0867-4","article-title":"Endothelial nitric oxide synthase transgenic models of endothelial dysfunction","volume":"460","author":"Atochin","year":"2010","journal-title":"Pflugers Arch."},{"key":"2024020508380782700_DMM050265C2","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/s004290050304","article-title":"Comparative anatomy and ontogeny of the ductus arteriosus, a vascular outsider","volume":"200","author":"Bergwerff","year":"1999","journal-title":"Anat. 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