title: Methionine-induced homocysteinemia impairs endothelial function in hypertensives: the role of asymmetrical dimethylarginine and antioxidant vitamins.
abstract: BACKGROUND
  Nitric oxide synthase (NOS) inhibitor asymmetrical dimethylarginine (ADMA) is synthesized by the methylation of arginine as part of the methionine/homocysteine cycle. However, the mechanisms regulating ADMA synthesis in hypertension are unclear.
  
  
  METHODS
  We investigated the role of ADMA and antioxidants in endothelial dysfunction during methionine-induced homocysteinemia in hypertensives. Thirty-nine hypertensives and forty-nine normotensive controls underwent methionine loading (100 mg methionine/kg BW), after being randomized to receive vitamin C (2 g) and E (800 IU) or placebo. Endothelium-dependent dilation (EDD) was evaluated by plethysmography (baseline and 4-h post-methionine loading (4-h PML)).
  
  
  RESULTS
  Hypertensives had higher homocysteine at baseline (P < 0.001) and 4-h PML (P < 0.05), whereas methionine increased homocysteine in all groups. EDD was decreased in both vitamins and placebo groups in controls (P < 0.01 for both) and vitamins- and placebo-treated hypertensives (P < 0.05 and P < 0.01, respectively). In controls, ADMA was increased in both vitamin- and placebo groups (P < 0.01 for both) at 4-h PML. Hypertensives had higher ADMA at baseline (P < 0.01 vs. normotensive) and remained unchanged at 4-h PML (P = NS in placebo and vitamins treated).
  
  
  CONCLUSIONS
  ADMA is elevated in hypertensives but remains unchanged after methionine loading, suggesting that ADMA plays an important role in endothelial dysfunction in hypertensives, but it is not responsible for homocysteine-induced endothelial dysfunction in these patients.
authors.affiliation: 1st Cardiology Department, Athens University Medical School, Athens, Greece. drtousoulis@hotmail.com
authors.forename: Dimitris
authors.initials: D
authors.lastname: Tousoulis
authors.forename: George
authors.initials: G
authors.lastname: Bouras
authors.forename: Charalambos
authors.initials: C
authors.lastname: Antoniades
authors.forename: Kyriakoula
authors.initials: K
authors.lastname: Marinou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papageorgiou
authors.forename: Antigoni
authors.initials: A
authors.lastname: Miliou
authors.forename: George
authors.initials: G
authors.lastname: Hatzis
authors.forename: Elli
authors.initials: E
authors.lastname: Stefanadi
authors.forename: Costas
authors.initials: C
authors.lastname: Tsioufis
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced* / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008715:Methionine; D008875:Middle Aged; D014664:Vasodilation / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D006710:Homocysteine; D014810:Vitamin E; C018524:N,N-dimethylarginine; D001120:Arginine; D008715:Methionine; D001205:Ascorbic Acid