Methionine-induced homocysteinemia impairs endothelial function in hypertensives: the role of asymmetrical dimethylarginine and antioxidant vitamins.
Tousoulis D., Bouras G., Antoniades C., Marinou K., Papageorgiou N., Miliou A., Hatzis G., Stefanadi E., Tsioufis C., Stefanadis C.
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.