Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans
Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans
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DOI：
10.1161/01.cir.103.12.1618
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发表时间：
2001-03-27
期刊：
影响因子：
37.8
通讯作者：
Creager, MA
中科院分区：
文献类型：
--
作者：
Beckman, JA;Goldfine, AB;Creager, MA
背景-胰岛素依赖型和非胰岛素依赖型糖尿病患者的内皮依赖性血管扩张功能受损，并通过服用维生素C恢复，这暗示氧化应激起致病作用。在健康受试者中，高血糖本身可减弱内皮依赖性血管扩张。因此，这项研究调查了非糖尿病人给予抗氧化剂维生素C是否能恢复由高血糖引起的内皮依赖性血管扩张。方法和结果：在正常血糖期间、动脉内注射葡萄糖(50%)造成的高血糖(300 mg/dL)6小时后以及在高血糖期间联合给予维生素C(24 mg/min)，测量内皮依赖性血管扩张。高血糖组血管内皮依赖性舒张功能明显减弱(P=0.02，方差分析)，维生素C可恢复内皮依赖性血管扩张功能(P=0.04)。相反，等摩尔的甘露醇输注并不影响血管内皮依赖性的舒张性，加或不加维生素C(P NS)。采用递增输注氯化维拉帕米(10~300ug/min)的方法测定非内皮依赖性血管舒张功能，并与N-G-单聚体-L-精氨酸(L-NMMA)联合应用。在无L-NMMA存在的情况下，高血糖时非内皮依赖性血管扩张功能无明显变化(P=NS)，但可被维生素C增强(P=0.04)。结论：维生素C对急性高血糖所致的内皮依赖性血管扩张有恢复作用。这些发现表明，高血糖可能部分通过产生超氧阴离子而导致血管功能受损。
Background-Endothelium-dependent vasodilation is impaired in patients with insulin-dependent and non-insulin-dependent diabetes mellitus and restored by vitamin C administration, implicating a causative role for oxidant stress. Hyperglycemia per se attenuates endothelium-dependent vasodilation;in healthy subjects. Accordingly, this study investigated whether impaired endothelium-dependent vasodilation caused by hyperglycemia in nondiabetic humans is restored by administration of the antioxidant vitamin C.Methods and Results-Endothelium-dependent vasodilation was measured by incremental brachial artery administration of methacholine chloride (0.3 to 10 mug/min) during euglycemia, after 6 hours of hyperglycemia (300 mg/dL) created by dextrose (50%) intra-arterial infusion, and with coadministration of vitamin C (24 mg/min) during hyperglycemia. Endothelium-dependent vasodilation was significantly diminished by hyperglycemia (P=0.02 by ANOVA) and restored by vitamin C (P=0.04). In contrast, endothelium-dependent vasodilation was not affected by equimolar infusions of mannitol, with and without vitamin C coinfusion (P NS). Endothelium-independent vasodilation was measured by incremental infusion of verapamil chloride (10 to 300 mug/min) without and with coadministration of N-G-monomerhyl-L-arginine (L-NMMA). In the absence of L-NMMA, endothelium-independent vasodilation was not significantly altered during hyperglycemia (P=NS) but was augmented by vitamin C (P=0.04). The coadministration of L-NMMA eliminated the vitamin C-related augmentation in verapamil-mediated vasodilation.Conclusions-Vitamin C administration restores endothelium-dependent vasodilation impaired by acute hyperglycemia in healthy humans in vivo. These findings suggest that hyperglycemia may contribute in part to impaired vascular function through production of superoxide anion.