Antioxidants and endothelial dysfunction in hyperlipidemia

被引:49
作者
Warnholtz A. [1 ]
Mollnau H. [1 ]
Oelze M. [1 ]
Wendt M. [1 ]
Münzel T. [1 ]
机构
[1] Universitätsklinik Eppendorf, Abteilung für Kardiologie, 20246 Hamburg
关键词
Nitric Oxide; Endothelial Dysfunction; Angiotensin Converting Enzyme; Angiotensin Converting Enzyme Inhibitor; Chronic Smoker;
D O I
10.1007/s11906-001-0081-z
中图分类号
学科分类号
摘要
Endothelial function is abnormal in a variety of diseased states such as hypercholesterolemia and atherosclerosis. This may be secondary to decreased synthesis of nitric oxide (NO) and/or increased degradation of NO due to interaction with superoxide anions. More recent experimental observations demonstrate increased production of superoxide in hyperlipidemia, suggesting that endothelial dysfunction in these states is in part secondary to increased NO metabolism. Enzymes proposed to be involved in increased superoxide production may include xanthine oxidase, the NO synthase, and the NAD(P)H oxidase. Superoxide rapidly reacts with NO to form peroxynitrite (ONOO-), a highly reactive intermediate with cytotoxic properties. Despite experimental evidence for the oxidative stress concept in causing endothelial dysfunction, the results of recent randomized trials to test the influence of antioxidants on coronary event rates and prognosis in patients with coronary artery disease were very disappointing. In all of these studies the use of vitamins such as vitamin E failed to improve the prognosis. In contrast, treatment with angiotensin converting enzyme inhibitors or cholesterollowering drugs improved endothelial dysfunction, prevented the activation of superoxide-producing enzymes in cholesterol-fed animals, reduced coronary event rates, and improved prognosis in patients with coronary artery disease. Therefore, inhibition of superoxide production at the enzymatic level rather than symptomatic superoxide scavenging may be the better choice of treatment. Copyright © 2001 by Current Science Inc.
引用
收藏
页码:53 / 60
页数:7
相关论文
共 62 条
[1]  
Schachinger V., Britten M.B., Zeiher A.M., Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease, Circulation, 101, pp. 1899-1906, (2000)
[2]  
Suwaidi J.A., Hamasaki S., Higano S.T., Et al., Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction, Circulation, 101, pp. 948-954, (2000)
[3]  
Palmer R.M., Ferrige A.G., Moncada S., Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor, Nature, 327, pp. 524-526, (1987)
[4]  
Myers P.R., Minor Jr. R.L., Guerra Jr. R., Et al., Vasor elaxa nt properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide, Nature, 345, pp. 161-163, (1990)
[5]  
Munzel T., Heitzer T., Harrison D.G., The physiology and pathophysiology of the nitric oxide/superoxide system, Herz, 22, pp. 158-172, (1997)
[6]  
Gryglewski R.J., Palmer R.M.J., Moncada S., Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor, Nature, 320, pp. 454-456, (1986)
[7]  
Beckman J.S., Beckman T.W., Chen J., Et al., Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide, Proc Natl Acad Sci U S A, 87, pp. 1620-1624, (1990)
[8]  
Freiman P.C., Mitchell G.C., Heistad D.D., Et al., Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates, Circ Res, 58, pp. 783-789, (1986)
[9]  
Ludmer P.L., Selwyn A.P., Shook T.L., Et al., Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries, N Engl J Med, 315, pp. 1046-1051, (1986)
[10]  
Zeiher A.M., Drexler H., Wollschlager H., Et al., Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis, Circulation, 83, pp. 391-401, (1991)