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Failure of flux through endothelial nitric oxide synthase (<jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>) contributes to increased vasoconstriction and decreased vasorelaxation. The underproduction of nitric oxide by <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content> is in part due to increased levels of asymmetric dimethylarginine (<jats:styled-content style=\"fixed-case\">ADMA<\/jats:styled-content>), an endogenous competitive inhibitor of nitric oxide synthase. The inhibitory effects of increased <jats:styled-content style=\"fixed-case\">ADMA<\/jats:styled-content> levels may be counteracted increasing serum <jats:sc>l<\/jats:sc>_arginine, which is often an effective treatment strategy in these patients. As such, <jats:sc>l<\/jats:sc>_arginine_based therapies should be considered in managing secondary <jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>, particularly given their favourable safety and tolerability profile. While there is no established dosing regimen, studies of oral <jats:sc>l<\/jats:sc>_arginine in secondary <jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content> suggest that divided dosing may begin at 1_2 g\/day and may be titrated up to 10 g\/day. Conversely, primary <jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content> is not associated with increased <jats:styled-content style=\"fixed-case\">ADMA<\/jats:styled-content> production which likely accounts for the failure of <jats:sc>l<\/jats:sc>_arginine trials to show benefit in primary RP.<\/jats:p>","DOI":"10.1111\/jdv.15180","type":"journal-article","created":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T16:07:24Z","timestamp":1531498044000},"page":"497-503","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The clinical effects of <scp>l<\/scp>_arginine and asymmetric dimethylarginine: implications for treatment in secondary Raynaud's phenomenon"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8850-6011","authenticated-orcid":false,"given":"P.","family":"Curtiss","sequence":"first","affiliation":[{"name":"Skin Lupus &amp; Autoimmune Connective Tissue Section The Ronald O. 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