title: Folic acid treatment reduces elevated plasma levels of asymmetric dimethylarginine in hyperhomocysteinaemic subjects.
abstract: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, has been suggested to be a novel risk factor for endothelial dysfunction. It has previously been reported that hyperhomocysteinaemia may be associated with impaired endothelium-dependent vasodilation and reduced plasma level of NO-derived endproducts (NOx). In the present study, plasma levels of arginine and ADMA were measured in twenty-one healthy control subjects, and in twenty-one hyperhomocysteinaemic subjects before and after 6 weeks and 12 months of folic acid supplementation, and compared with previously measured plasma NOx values in the hyperhomocysteinaemic subjects. Compared with control subjects, hyperhomocysteinaemic subjects had higher plasma levels of arginine and ADMA. More importantly, folic acid therapy significantly reduced plasma levels of arginine and ADMA. Furthermore, plasma levels of arginine and ADMA were positively correlated with plasma homocysteine levels and negatively correlated with plasma folate, as well as negatively correlated with plasma NOx. Our results suggest that ADMA may be a mediator of the atherogenic effects of homocysteine.
authors.affiliation: Research Institute for Internal Medicine, University Hospital Rikshospitalet, Oslo, Norway. kirsten.holven@basalmed.uio.no
authors.forename: Kirsten B
authors.initials: KB
authors.lastname: Holven
authors.forename: Tor S
authors.initials: TS
authors.lastname: Haugstad
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Holm
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Leiv
authors.initials: L
authors.lastname: Ose
authors.forename: Marit S
authors.initials: MS
authors.lastname: Nenseter
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D019587:Dietary Supplements; D004791:Enzyme Inhibitors / Q000097:blood*; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D006710:Homocysteine; C018524:N,N-dimethylarginine; D005492:Folic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase