1st Cardiology Department, Athens University Medical School, Athens, Greece.
Am J Hypertens. 2011 Aug;24(8):936-42. doi: 10.1038/ajh.2011.65. Epub 2011 Apr 14.
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.
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)).
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).
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.
一氧化氮合酶（NOS）抑制剂不对称二甲基精氨酸（ADMA）是作为蛋氨酸/同型半胱氨酸循环的一部分由精氨酸甲基化合成的。然而，调节高血压中 ADMA 合成的机制尚不清楚。
我们研究了 ADMA 和抗氧化剂在蛋氨酸诱导的高同型半胱氨酸血症中高血压患者内皮功能障碍中的作用。39 名高血压患者和 49 名血压正常的对照者接受蛋氨酸负荷（100mg 蛋氨酸/kgBW），并随机接受维生素 C（2g）和 E（800IU）或安慰剂。通过体积描记法（基线和蛋氨酸负荷后 4 小时（4-h PML））评估内皮依赖性舒张（EDD）。
高血压患者基线时（P < 0.001）和 4-h PML 时（P < 0.05）同型半胱氨酸水平较高，而所有组的蛋氨酸均增加了同型半胱氨酸。对照组中，两种维生素和安慰剂组的 EDD 均降低（两组均 P < 0.01），维生素和安慰剂治疗的高血压患者 EDD 也降低（两组均 P < 0.05 和 P < 0.01）。在对照组中，两种维生素和安慰剂组在 4-h PML 时 ADMA 均增加（两组均 P < 0.01）。高血压患者基线时 ADMA 水平较高（与血压正常者相比 P < 0.01），4-h PML 时无变化（安慰剂和维生素治疗时 P = NS）。
ADMA 在高血压患者中升高，但蛋氨酸负荷后无变化，提示 ADMA 在高血压患者内皮功能障碍中起重要作用，但不是这些患者同型半胱氨酸诱导的内皮功能障碍的原因。
