Beckman J A, Goldfine A B, Gordon M B, Creager M A
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
Circulation. 2001 Mar 27;103(12):1618-23. doi: 10.1161/01.cir.103.12.1618.
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.
Endothelium-dependent vasodilation was measured by incremental brachial artery administration of methacholine chloride (0.3 to 10 microg/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 microg/min) without and with coadministration of N:(G)-monomethyl-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.
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.
胰岛素依赖型和非胰岛素依赖型糖尿病患者存在内皮依赖性血管舒张功能受损的情况，补充维生素C后该功能可恢复，这表明氧化应激起了致病作用。高血糖本身会削弱健康受试者的内皮依赖性血管舒张功能。因此，本研究调查了非糖尿病患者因高血糖导致的内皮依赖性血管舒张功能受损是否可通过补充抗氧化剂维生素C得以恢复。
通过在正常血糖期间、经动脉输注50%葡萄糖造成6小时高血糖（300mg/dL）后以及高血糖期间同时补充维生素C（24mg/min）时，递增剂量肱动脉注射氯化乙酰甲胆碱（0.3至10μg/min）来测量内皮依赖性血管舒张功能。高血糖显著削弱了内皮依赖性血管舒张功能（方差分析P=0.02），而维生素C使其恢复（P=0.04）。相比之下，等摩尔输注甘露醇，无论是否同时输注维生素C，对内皮依赖性血管舒张功能均无影响（P=无显著性差异）。通过递增剂量输注维拉帕米氯化物（10至300μg/min），在不使用和使用N(G)-单甲基-L-精氨酸（L-NMMA）的情况下测量非内皮依赖性血管舒张功能。在不使用L-NMMA时，高血糖期间非内皮依赖性血管舒张功能无显著改变（P=无显著性差异），但维生素C使其增强（P=0.04）。同时使用L-NMMA消除了维生素C相关的维拉帕米介导的血管舒张增强作用。
补充维生素C可恢复健康人体内因急性高血糖而受损的内皮依赖性血管舒张功能。这些发现表明，高血糖可能部分通过超氧阴离子的产生导致血管功能受损。
