Tetrahydrobiopterin improves endothelial function in patients with coronary artery disease
Tetrahydrobiopterin improves endothelial function in patients with coronary artery disease
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DOI：
10.1097/00005344-200002000-00001
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发表时间：
2000-02-01
影响因子：
3
通讯作者：
Lüscher, TF
中科院分区：
文献类型：
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作者：
Maier, W;Cosentino, F;Lüscher, TF
四氢生物蝶呤 (BH(4)) 是一氧化氮合酶 (NOS) 的重要辅助因子，也是氧自由基的清除剂。在体外条件下，BH(4) 可用性的降低会导致一氧化氮 (NO) 产生减少和超氧化物形成增加。我们研究了外源性 BH(4) 对冠状动脉疾病患者血管造影正常血管段内皮功能的影响。 19 名冠状动脉疾病患者接受了定量冠状动脉造影，同时测量冠状动脉现速 (Cardiometrics FloWire)。在基线时、冠状动脉内（i.c）给予乙酰胆碱（Ach；10(-4)M）、输注BH（4）（10（-2）M）后以及同时输注ACh和BH（4）后，在左冠状动脉的血管造影正常段中获得数据。研究结束时，注射 300 μg 硝酸甘油 (NTG)。施用以获得最大的血管舒张。在每个步骤中，在注射 18 μg 腺苷之前和之后测定流速。评估冠状动脉血流速度储备。在 15 名患者中，ACh 引起 -18 +/- 3% 的冠状血管收缩（内皮功能障碍；与基线相比，p < 0.0001），在 4 名患者中，血管舒张为 +39 +/- 20%。在 15 名患有内皮功能障碍的患者中，单独使用 BH(4) 不会影响血管面积，但可以防止 ACh 血管收缩（+2 +/- 3%，NS，与基线相比）。相应地，计算的体积流量在ACh和BH(4)共输注后显示出最高值。在不同的输注步骤期间，冠状动脉血流速度储备是相当的。 BH(4) 可预防冠状动脉疾病患者血管造影正常血管的 ACh 诱导的血管收缩。因此，替代 NOS 辅助因子可能代表治疗内皮功能障碍的新方法。
Tetrahydrobiopterin (BH(4)) is an essential cofactor for nitric oxide:synthase (NOS) and a scavenger of oxygen-derived free radicals. Decreased availability of BH(4) leads, under in vitro conditions, to reduced nitric oxide (NO) production and increased superoxide formation. We studied the effect of exogenous BH(4) on endothelial function of angiographically normal vessel segments in patients with coronary artery disease. Nineteen patients with coronary artery disease underwent quantitative coronary angiography with simultaneous coronary now velocity measurements (Cardiometrics FloWire). Data were obtained in angiographically normal segments of the left coronary artery at baseline, after intracoronary (i.c.) administration of acetylcholine (Ach; 10(-4) M), after infusion of BH(4) (10(-2) M), and after co-infusion of ACh and BH(4). At the end of the study, 300 mu g nitroglycerin (NTG) i.c. was administered to obtain maximal vasodilation. At each step, flow velocity was determined before and after 18 mu g adenosine i.c. to assess coronary flow velocity reserve. In 15 patients, ACh induced coronary vasoconstriction of -18 +/- 3% (endothelial dysfunction; p < 0.0001 vs. baseline), and in four patients, vasodilation of +39 +/- 20%. In the 15 patients with endothelial dysfunction, BH(4) alone did not influence vessel area but prevented vasoconstriction to ACh (+2 +/- 3%, NS, vs. baseline). Correspondingly, calculated volume flow showed the highest value after co-infusion of ACh and BH(4). Coronary flow velocity reserve was comparable during the various infusion steps. BH(4) pre vents ACh-induced vasoconstriction of angiographically normal vessels in patients with coronary artery disease. Thus substitution of this cofactor of NOS may represent a new approach for the treatment of endothelial dysfunction.