Goonasekera C D, Rees D D, Woolard P, Frend A, Shah V, Dillon M J
Institute of Child Health and Great Ormond Street Children's Hospital NHS Trust, London, UK.
J Hypertens. 1997 Aug;15(8):901-9. doi: 10.1097/00004872-199715080-00015.
To establish the role played by the circulating nitric oxide synthase inhibitors N(G)-monomethyl-L-arginine (L-NMMA), asymmetrical dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA) and its association with hypertension of children and adolescents.
We measured plasma concentrations of L-NMMA, ADMA and SDMA in 38 hypertensives (median age 7.7 years) and in nine healthy normotensive controls (median age 8.2 years) using high-performance liquid chromatography. In addition, their plasma renin activity was determined. The subjects' glomerular filtration rates were calculated from plasma creatinine and height measurements. To determine the vasoactive potency of the arginine analogues, concentration-response curves were plotted for the responses in isolated endothelium-intact and endothelium-denuded mouse aortic rings that had been pre-contracted by administration of a threshold concentration of phenylephrine.
Plasma ADMA and SDMA concentrations in members of the hypertensive group [0.23 +/- 0.03 and 1.37 +/- 0.06 micromol/l, respectively (means +/- SEM)] were significantly higher than those in members of the control group (ADMA 0.10 +/- 0.01 micromol/l and SDMA 1.18 +/- 0.06 micromol/l). Plasma concentrations of L-NMMA were similar in members of the hypertensive (0.21 +/- 0.01 micromol/l) and control (0.18 +/- 0.02 micromol/l) groups. The glomerular filtration rate of the hypertensive group was below normal [70.4 +/- 5.4 ml/min per 1.73 m2 (mean +/- SEM)] and was significantly associated with elevated plasma concentrations of ADMA (r = -0.77, P < 0.001), SDMA (r = -0.38, P = 0.02) and L-NMMA (r = 0.35, P = 0.03). Higher plasma ADMA concentrations were associated with a lower plasma renin activity (r = -0.36, P = 0.04). The vasoactive potencies of ADMA (concentration for half-maximal effect with the endothelium intact 25.4 +/- 7.1 micromol/l) and L-NMMA (concentration for half-maximal effect with the endothelium intact 8.2 +/- 2.9 micromol/l) was significantly (P < 0.05) greater than that of SDMA. Both ADMA and L-NMMA (at 3 micromol/l concentrations) initiated a significant vasocontractile response from baseline (P = 0.03 and P < 0.001, respectively). These effects were absent after the endothelium had been removed. SDMA had no effect.
Plasma ADMA and SDMA levels are increased in hypertensive children. By inference from in-vitro data, ADMA appears to attain sufficient concentrations to produce a significant change in vascular tone and hence might play a role in the pathophysiology of childhood hypertension.
确定循环中的一氧化氮合酶抑制剂N(G)-单甲基-L-精氨酸（L-NMMA）、不对称二甲基精氨酸（ADMA）和对称二甲基精氨酸（SDMA）所起的作用及其与儿童和青少年高血压的关联。
我们使用高效液相色谱法测量了38名高血压患者（中位年龄7.7岁）和9名健康血压正常对照者（中位年龄8.2岁）血浆中L-NMMA、ADMA和SDMA的浓度。此外，还测定了他们的血浆肾素活性。根据血浆肌酐和身高测量值计算受试者的肾小球滤过率。为了确定精氨酸类似物的血管活性效力，绘制了在预先用阈浓度去氧肾上腺素预收缩的完整内皮和去内皮小鼠主动脉环中的反应的浓度-反应曲线。
高血压组成员的血浆ADMA和SDMA浓度[分别为0.23±0.03和1.37±0.06 μmol/l（均值±标准误）]显著高于对照组成员（ADMA为0.10±0.01 μmol/l，SDMA为1.18±0.06 μmol/l）。高血压组（0.21±0.01 μmol/l）和对照组（0.18±0.02 μmol/l）成员的血浆L-NMMA浓度相似。高血压组的肾小球滤过率低于正常水平[70.4±5.4 ml/min per 1.73 m2（均值±标准误）]，且与血浆ADMA浓度升高（r = -0.77，P < 0.001）、SDMA浓度升高（r = -0.38，P = 0.02）和L-NMMA浓度升高（r = 0.35，P = 0.03）显著相关。较高的血浆ADMA浓度与较低的血浆肾素活性相关（r = -0.36，P = 0.04）。ADMA（完整内皮时半数最大效应浓度为25.4±7.1 μmol/l）和L-NMMA（完整内皮时半数最大效应浓度为8.2±2.9 μmol/l）的血管活性效力显著（P < 0.05）高于SDMA。ADMA和L-NMMA（浓度为3 μmol/l时）均引起相对于基线的显著血管收缩反应（分别为P = 0.03和P < 0.001）。去除内皮后这些效应消失。SDMA无作用。
高血压儿童血浆ADMA和SDMA水平升高。根据体外数据推断，ADMA似乎能达到足以引起血管张力显著变化的浓度，因此可能在儿童高血压的病理生理学中起作用。
