Premium
The clinical effects of l _arginine and asymmetric dimethylarginine: implications for treatment in secondary Raynaud's phenomenon
Author(s) -
Curtiss P.,
Schwager Z.,
Lo Sicco K.,
Franks A.G.
Publication year - 2019
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.15180
Subject(s) - asymmetric dimethylarginine , nitric oxide , medicine , enos , tolerability , arginine , nitric oxide synthase , pharmacology , biochemistry , adverse effect , chemistry , amino acid
Secondary Raynaud's phenomenon ( RP ) is often the sentinel clinical finding in systemic sclerosis and may precede systemic disease by several years. Altered nitric oxide metabolism plays a critical role in both fibrosis and severe secondary RP phenotypes in these patients. Increased flux through inducible nitric oxide synthase ( iNOS ) drives cutaneous fibrosis. Failure of flux through endothelial nitric oxide synthase ( eNOS ) contributes to increased vasoconstriction and decreased vasorelaxation. The underproduction of nitric oxide by eNOS is in part due to increased levels of asymmetric dimethylarginine ( ADMA ), an endogenous competitive inhibitor of nitric oxide synthase. The inhibitory effects of increased ADMA levels may be counteracted increasing serum l _arginine, which is often an effective treatment strategy in these patients. As such, l _arginine_based therapies should be considered in managing secondary RP , particularly given their favourable safety and tolerability profile. While there is no established dosing regimen, studies of oral l _arginine in secondary RP suggest that divided dosing may begin at 1_2 g/day and may be titrated up to 10 g/day. Conversely, primary RP is not associated with increased ADMA production which likely accounts for the failure of l _arginine trials to show benefit in primary RP.