Casino P R, Kilcoyne C M, Quyyumi A A, Hoeg J M, Panza J A
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Am Coll Cardiol. 1994 Mar 15;23(4):844-50. doi: 10.1016/0735-1097(94)90628-9.
The purpose of this study was to determine whether the impaired endothelium-dependent vasodilation of hypercholesterolemic patients is due to decreased availability of L-arginine, the substrate for nitric oxide.
Patients with hypercholesterolemia have impaired endothelium-dependent vasodilation that is related to a defect in the endothelium-derived nitric oxide system. However, the precise location of this abnormality has not been determined.
The study included 12 hypercholesterolemic patients (6 men, 6 women; 52 +/- 9 years old; serum cholesterol > 240 mg/dl) and 15 normal volunteers (8 men, 7 women; 50 +/- 6 years old; serum cholesterol < 210 mg/dl). The forearm vascular responses to intraarterial infusion of acetylcholine, an endothelium-dependent vasodilator (7.5, 15, 30 micrograms/min), and sodium nitroprusside, a direct smooth muscle dilator (0.8, 1.6, 3.2 micrograms/min) were studied before and during infusion of L- or D-arginine (a stereoisomer of arginine that is not a nitric oxide precursor).
The response to acetylcholine was lower in hypercholesterolemic patients than in control subjects. However, no significant difference was observed with sodium nitroprusside infusion. L-Arginine augmented the response to acetylcholine in normal subjects (maximal blood flow increased from 14.4 +/- 7 to 18.9 +/- 10 ml/min per 100 ml, p < 0.002). In contrast, in the hypercholesterolemic patients, only a mild but not significant improvement in the response to acetylcholine was observed with the infusion of L-arginine (maximal blood flow increased from 6.8 +/- 4 to 8.4 +/- 5 ml/min per 100 ml; p = 0.16); however, a similar mild but not significant change was also observed with D-arginine (maximal blood flow increased from 6.8 +/- 4 to 8.3 +/- 4 ml/min per 100 ml, p = 0.07). L-Arginine did not modify the response to sodium nitroprusside in either group.
The augmentation of endothelium-dependent vasodilation by L-arginine, the nitric oxide precursor, is defective in hypercholesterolemic patients. This supports the concept of an abnormal endothelium-derived nitric oxide system in hypercholesterolemia and indicates that decreased availability of nitric oxide substrate is not responsible for the impaired endothelial function in this condition.
本研究旨在确定高胆固醇血症患者内皮依赖性血管舒张功能受损是否归因于一氧化氮底物L-精氨酸的可用性降低。
高胆固醇血症患者存在内皮依赖性血管舒张功能受损，这与内皮源性一氧化氮系统缺陷有关。然而，这种异常的确切位置尚未确定。
该研究纳入了12例高胆固醇血症患者（6例男性，6例女性；年龄52±9岁；血清胆固醇>240mg/dl）和15名正常志愿者（8例男性，7例女性；年龄50±6岁；血清胆固醇<210mg/dl）。在输注L-精氨酸或D-精氨酸（精氨酸的一种立体异构体，不是一氧化氮前体）之前和期间，研究了前臂血管对动脉内输注内皮依赖性血管舒张剂乙酰胆碱（7.5、15、30微克/分钟）和直接平滑肌舒张剂硝普钠（0.8、1.6、3.2微克/分钟）的反应。
高胆固醇血症患者对乙酰胆碱的反应低于对照组。然而，输注硝普钠时未观察到显著差异。L-精氨酸增强了正常受试者对乙酰胆碱的反应（最大血流量从每100ml 14.4±7增加到18.9±10ml/分钟，p<0.002）。相比之下，在高胆固醇血症患者中，输注L-精氨酸时，仅观察到对乙酰胆碱反应有轻微但不显著的改善（最大血流量从每100ml 6.8±4增加到8.4±5ml/分钟；p=0.16）；然而，输注D-精氨酸时也观察到类似的轻微但不显著的变化（最大血流量从每100ml
