Chen X, Touyz R M, Park J B, Schiffrin E L
Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada.
Hypertension. 2001 Sep;38(3 Pt 2):606-11. doi: 10.1161/hy09t1.094005.
Ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) have antioxidant properties that could improve redox-sensitive vascular changes associated with hypertension. We determined whether vitamins C and E influence vascular function and structure in hypertension by modulating activity of NADPH oxidase and superoxide dismutase (SOD). Adult stroke-prone spontaneously hypertensive rats (SHRSP) were divided into 3 groups: control (C; n=6), vitamin C-treated (vit C, 1000 mg/day; n=7), and vitamin E-treated (vit E, 1000 IU/day; n=8). All rats were fed 4% NaCl. Blood pressure was measured weekly. After 6 weeks of treatment, the rats were killed, and mesenteric arteries were mounted as pressurized preparations. Vascular O(2)(-) generation and NADPH oxidase activity were measured by chemiluminescence. Vascular SOD activity and plasma total antioxidant status (TAS) were determined spectrophotometrically. Blood pressure increased from 212+/-7 to 265+/-6 mm Hg in controls. Treatment prevented progression of hypertension (vit C, 222+/-6 to 234+/-14 mm Hg; vit E, 220+/-9 to 227+/-10 mm Hg). Acetylcholine-induced vasodilation was improved (P<0.05), and media-to-lumen ratio was reduced (P<0.05) in the treated rats. O(2)(-) was lower in vitamin-treated groups compared with controls (vit C, 10+/-4 nmol. min(-1). g(-1) dry tissue weight; vit E, 9.6+/-3.5 nmol. min(-1). g(-1) dry tissue weight; C, 21+/-9 nmol. min(-1). g(-1) dry tissue weight; P<0.05). Both vitamin-treated groups showed significant improvement (P<0.01) in TAS. These effects were associated with decreased activation of vascular NADPH oxidase (vit C, 46+/-10; vit E, 50+/-9; C, 70+/-16 nmol. min(-1). g(-1) dry tissue weight, P<0.05) and increased activation of SOD (vit C, 12+/-2; vit E, 8+/-1; C, 4.6+/-1 U/mg; P<0.05). Our results demonstrate that vitamins C and E reduce oxidative stress, improve vascular function and structure, and prevent progression of hypertension in SHRSP. These effects may be mediated via modulation of enzyme systems that generate free radicals.
抗坏血酸（维生素C）和α-生育酚（维生素E）具有抗氧化特性，可能改善与高血压相关的氧化还原敏感型血管变化。我们通过调节烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶和超氧化物歧化酶（SOD）的活性，来确定维生素C和E是否会影响高血压患者的血管功能和结构。将成年易中风自发性高血压大鼠（SHRSP）分为3组：对照组（C；n = 6）、维生素C治疗组（维生素C，1000毫克/天；n = 7）和维生素E治疗组（维生素E，1000国际单位/天；n = 8）。所有大鼠均喂食4%的氯化钠。每周测量血压。治疗6周后，处死大鼠，将肠系膜动脉制成压力制剂。通过化学发光法测量血管超氧阴离子（O₂⁻）生成和NADPH氧化酶活性。用分光光度法测定血管SOD活性和血浆总抗氧化状态（TAS）。对照组血压从212±7毫米汞柱升至265±6毫米汞柱。治疗可预防高血压进展（维生素C组，从222±6毫米汞柱升至234±14毫米汞柱；维生素E组，从220±9毫米汞柱升至227±10毫米汞柱）。治疗组大鼠乙酰胆碱诱导的血管舒张得到改善（P<0.05），中膜与管腔比值降低（P<0.05）。与对照组相比，维生素治疗组的O₂⁻水平较低（维生素C组，10±4纳摩尔·分钟⁻¹·克⁻¹干组织重量；维生素E组，9.6±3.5纳摩尔·分钟⁻¹·克⁻¹干组织重量；C组，21±9纳摩尔·分钟⁻¹·克⁻¹干组织重量；P<0.05）。两个维生素治疗组的TAS均有显著改善（P<0.01）。这些作用与血管NADPH氧化酶激活减少（维生素C组，46±10；维生素E组，50±9；C组，70±16纳摩尔·分钟⁻¹·克⁻¹干组织重量，P<0.05）和SOD激活增加（维生素C组，12±2；维生素E组，8±1；C组，4.6±1单位/毫克；P<0.05）有关。我们的结果表明，维生素C和E可降低氧化应激，改善血管功能和结构，并预防SHRSP高血压的进展。这些作用可能是通过调节产生自由基的酶系统介导的。
