Lerman A, Burnett J C, Higano S T, McKinley L J, Holmes D R
Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minn. 55905, USA.
Circulation. 1998 Jun 2;97(21):2123-8. doi: 10.1161/01.cir.97.21.2123.
Coronary endothelial dysfunction is characterized by an imbalance between endothelium-derived vasodilating and vasoconstricting factors and coronary vasoconstriction in response to the endothelium-dependent vasodilator acetylcholine. Thus, the present double-blind, randomized study was designed to test the hypothesis that long-term, 6-month supplementation of L-arginine, the precursor of the endothelium-derived vasodilator NO, reverses coronary endothelial dysfunction to acetylcholine in humans with nonobstructive coronary artery disease.
Twenty-six patients without significant coronary artery disease on coronary angiography and intravascular ultrasound were blindly randomized to either oral L-arginine or placebo, 3 g TID. Endothelium-dependent coronary blood flow reserve to acetylcholine (10(-6) to 10(-4) mol/L) was assessed at baseline and after 6 months of therapy. There was no difference between the two study groups in clinical characteristics or in the coronary blood flow in the response to acetylcholine at baseline. After 6 months, the coronary blood flow in response to acetylcholine in the subjects who were taking L-arginine increased compared with the placebo group (149 +/- 20% versus 6 +/- 9%, P < 0.05). This was associated with a decrease in plasma endothelin concentrations and an improvement in patients' symptoms scores in the L-arginine treatment group compared with the placebo group.
Long-term oral L-arginine supplementation for 6 months in humans improves coronary small-vessel endothelial function in association with a significant improvement in symptoms and a decrease in plasma endothelin concentrations. This study proposes a role for L-arginine as a therapeutic option for patients with coronary endothelial dysfunction and nonobstructive coronary artery disease.
冠状动脉内皮功能障碍的特征是内皮源性血管舒张因子和血管收缩因子之间失衡，以及对内皮依赖性血管舒张剂乙酰胆碱产生冠状动脉血管收缩反应。因此，本双盲随机研究旨在检验以下假设：对于非阻塞性冠状动脉疾病患者，长期（6个月）补充内皮源性血管舒张剂一氧化氮（NO）的前体L-精氨酸可逆转其对乙酰胆碱的冠状动脉内皮功能障碍。
26例冠状动脉造影和血管内超声检查显示无明显冠状动脉疾病的患者被随机分为两组，分别口服L-精氨酸或安慰剂，每日3次，每次3 g。在基线和治疗6个月后评估对乙酰胆碱（10⁻⁶至10⁻⁴mol/L）的内皮依赖性冠状动脉血流储备。两个研究组在临床特征或基线时对乙酰胆碱的冠状动脉血流方面无差异。6个月后，服用L-精氨酸的受试者对乙酰胆碱的冠状动脉血流较安慰剂组增加（149±20%对6±9%，P<0.05）。与安慰剂组相比，这与L-精氨酸治疗组血浆内皮素浓度降低及患者症状评分改善有关。
人类长期（6个月）口服L-精氨酸可改善冠状动脉小血管内皮功能，同时症状显著改善，血浆内皮素浓度降低。本研究提出L-精氨酸可作为冠状动脉内皮功能障碍和非阻塞性冠状动脉疾病患者的一种治疗选择。
