VASC. EFFECTS OF ORAL L-ARGININE THERAPY IN PTS WITH CAD ON CONVENTIONAL MED MGT

一氧化氮（NO）生物活性在冠状动脉疾病（CAD）患者的冠状动脉和全身循环中降低。我们的目的是确定l -精氨酸（一氧化氮合成的底物）是否能改善冠心病患者在适当医疗管理下血管内皮的稳态功能，从而可能成为治疗冠心病的有用辅助疗法。30例冠心病患者（男性29例，平均年龄67+/-8岁），经适当治疗后症状稳定。在一项随机双盲研究中，在l -精氨酸9 gm或安慰剂治疗1个月后进行测试，在停止治疗1个月后交叉到替代治疗。采用化学发光技术测定硝酸限制饮食条件下血清中氮氧化物水平，作为内皮NO释放指标；采用超声法测定前臂缺血后肱动脉血流介导的扩张水平，作为内皮NO生物活性指标；采用血清中可溶性细胞粘附分子水平，作为NO调节炎症标志物指标。与安慰剂相比，L-精氨酸治疗增加了L-精氨酸血浆水平（平均+/-SD: 130+/-53 vs 70+/-17微mol/L， P=0.0001）。然而，血清氮氧化物（19.3+/-7.9 vs. 18.6+/-6.7 μ mol/L， P=0.55）、血流介导的舒张（11.9+/-6.3 vs.11.4+/-7.9%， P=0.74）、血清e-选择素水平（47.8+/-15.2 vs. 47.2+/-14.4 ng/mL， P=0.60）、细胞间黏附分子-1 （250+/-57 vs. 249+/-57 ng/mL， P=0.86）和血管细胞黏附分子-1 （567+/-124 vs. 574+/-135 ng/mL， P=0.47）均无显著差异。我们得出结论，口服l -精氨酸治疗在适当的医疗管理下可能不会增加CAD患者内皮NO释放或生物活性。因此，这种治疗方法可能对这组患者没有动脉粥样硬化保护作用。- L-精氨酸，一氧化氮，内皮依赖，化学发光技术。人体受试者

Nitric Oxide (NO) bioactivity is reduced in the coronary and systemic circulations of patients with coronary artery disease (CAD). Our purpose was to determine whether L-arginine, the substrate for NO synthesis, improves homeostatic functions of the vascular endothelium in patients with CAD mantained on appropriate medical management, and thus might be useful adjunctive therapy in the management of their disease. Thirty patients (29 men, average age 67+/-8 years) with CAD and stable symptoms on appropriate medical management participated in this study. Testing was performed after 1 month of L-arginine 9 gm or placebo, with crossover to the alternate therapy after 1 month off therapy in a randomized, double-blind study. Nitrogen oxides in serum were measured (chemiluminescence technique)on a nitrate-restricted diet as an index of endothelial NO release, brachial artery flow-mediated dilation was measured by ultrasound following forearm ischemia as an index of endothelial NO bioactivity, and soluble cell adhesion molecules were measured in serum as an index of NO-regulated inflammatory markers. Compared with placebo, L-arginine therapy increased plasma levels of L-arginine (mean+/-SD: 130+/-53 vs. 70+/-17 micromol/L, P=0.0001). However, there were no significant differences in serum nitrogen oxides (19.3+/-7.9 vs. 18.6+/-6.7 micromol/L, P=0.55), flow-mediated dilation (11.9+/-6.3 vs.11.4+/-7.9%, P=0.74), or serum levels of E-selectin (47.8+/-15.2 vs. 47.2+/-14.4 ng/mL, P=0.60), intercellular adhesion molecule-1 (250+/-57 vs. 249+/-57 ng/mL, P=0.86), and vascular cell adhesion molecule-1 (567+/-124 vs. 574+/-135 ng/mL, P=0.47). We conclude that oral L-arginine therapy may not augment endothelial NO release or bioactivity in CAD patients on appropriate medical management. Accordingly, this therapeutic approach may not be of atheroprotective benefit to this group of patients. - L- arginine, nitric oxide, endothelium-dependent, chemiluminescence technique - Human Subjects