Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia.
Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia.
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DOI：
10.1161/01.cir.95.12.2617
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发表时间：
1997-06
期刊：
影响因子：
37.8
通讯作者：
H. Ting;Farris K Timimi;Elizabeth A. Haley;M. Roddy;P. Ganz;M. Creager
中科院分区：
文献类型：
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作者：
H. Ting;Farris K Timimi;Elizabeth A. Haley;M. Roddy;P. Ganz;M. Creager
高胆固醇血症患者的内皮依赖性血管舒张功能受损。内皮源性一氧化氮的氧化降解在高胆固醇血症动物模型的内皮功能障碍中起主要作用。为了评估这种机制是否与人类有关，我们研究了维生素C（一种抗氧化剂）对高胆固醇血症患者前臂阻力血管扩张功能的影响。方法和结果我们研究了11名高胆固醇血症和12名健康对照者。前臂血流量通过静脉闭塞体积描记法测定。通过动脉内输注乙酰甲胆碱（0.3至10微克/分钟）评估内皮依赖性血管舒张。通过动脉内输注硝普钠（0.3至10微克/分钟）和维拉帕米（10至300微克/分钟）测量内皮非依赖性血管舒张。前臂血流量的剂量反应曲线，确定每种药物之前和期间共同管理的维生素C（24毫克/分钟）。在高胆固醇血症受试者中，乙酰甲胆碱的内皮依赖性血管舒张作用通过联合输注维生素C而增强（P = 0.001）;相反，硝普钠和维拉帕米的内皮非依赖性血管舒张作用不受联合输注维生素C的影响（分别为P = 0.8和P = 0.3）。在对照组中，维生素C给药没有改变内皮依赖性血管舒张（P =.2）。结论：我们得出结论，维生素C改善高胆固醇血症患者前臂阻力血管内皮依赖性血管舒张。这些研究结果表明，一氧化氮降解氧衍生的自由基有助于异常血管反应性高胆固醇血症的人。
BACKGROUND Endothelium-dependent vasodilation is impaired in humans with hypercholesterolemia. Oxidative degradation of endothelium-derived nitric oxide plays a major role in endothelial dysfunction in animal models of hypercholesterolemia. To assess whether this mechanism is relevant to humans, we studied the effect of vitamin C, an antioxidant, on vasodilator function in forearm resistance vessels of patients with hypercholesterolemia. METHODS AND RESULTS We studied 11 hypercholesterolemic and 12 healthy control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intra-arterial infusion of methacholine (0.3 to 10 micrograms/min). Endothelium-independent vasodilation was measured by intra-arterial infusion of nitroprusside (0.3 to 10 micrograms/min) and verapamil (10 to 300 micrograms/min). Forearm blood flow dose-response curves were determined for each drug before and during coadministration of vitamin C (24 mg/min). In hypercholesterolemic subjects, endothelium-dependent vasodilation to methacholine was augmented by coinfusion of vitamin C (P = .001); in contrast, endothelium-independent vasodilation to nitroprusside and verapamil were not affected by coinfusion of vitamin C (P = .8 and P = .3, respectively). In control subjects, vitamin C administration did not alter endothelium-dependent vasodilation (P = .2). CONCLUSIONS We conclude that vitamin C improves endothelium-dependent vasodilation in the forearm resistance vessels of patients with hypercholesterolemia. These findings suggest that nitric oxide degradation by oxygen-derived free radicals contributes to abnormal vascular reactivity in hypercholesterolemic humans.