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(Circulation. 1996;94:6-9.)
© 1996 American Heart Association, Inc.
Articles |
Antioxidant Vitamin C Improves Endothelial Dysfunction in Chronic Smokers
the Medizinische Klinik III, Kardiologie, Universitat Freiburg, Germany.
Correspondence to Thomas Munzel, MD, Universitatskrankenhaus Eppendorf, Abteilung fur Kardiologie, Martinistr 55, 20246 Hamburg, FRG.
Background Chronic smoking is associated with endothelial dysfunction, an early stage of atherosclerosis. It has been suggested that endothelial dysfunction may be a consequence of enhanced degradation of nitric oxide secondary to formation of oxygen-derived free radicals. To test this hypothesis, we investigated the effects of the antioxidant vitamin C on endothelium-dependent responses in chronic smokers.
Methods and Results Forearm blood flow responses to the endothelium-dependent vasodilator acetylcholine (7.5, 15, 30, and 60 µg/min) and the endothelium-independent vasodilator sodium nitroprusside (1, 3, and 10 µg/min) were measured by venous occlusion plethysmography in 10 control subjects and 10 chronic smokers. Drugs were infused into the brachial artery, and forearm blood flow was measured for each drug before and during concomitant intra-arterial infusion of the antioxidant vitamin C (18 mg/min). In control subjects, vitamin C had no effect on forearm blood flow in response to acetylcholine and sodium nitroprusside. In contrast, in chronic smokers the attenuated forearm blood flow responses to acetylcholine were markedly improved by concomitant administration of vitamin C, whereas the vasodilator responses to sodium nitroprusside were not affected.
Conclusions The present studies demonstrate that the antioxidant vitamin C markedly improves endothelium-dependent responses in chronic smokers. This observation supports the concept that endothelial dysfunction in chronic smokers is at least in part mediated by enhanced formation of oxygen-derived free radicals.
Key Words: smoking • endothelium • free radicals • antioxidants
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P. Minuz, G. Andrioli, M. Degan, S. Gaino, R. Ortolani, R. Tommasoli, V. Zuliani, A. Lechi, and C. Lechi The F2-Isoprostane 8-Epiprostaglandin F2{alpha} Increases Platelet Adhesion and Reduces the Antiadhesive and Antiaggregatory Effects of NO Arterioscler. Thromb. Vasc. Biol., August 1, 1998; 18(8): 1248 - 1256. [Abstract] [Full Text] [PDF]
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R. Campisi, J. Czernin, H. Schoder, J. W. Sayre, F. D. Marengo, M. E. Phelps, and H. R. Schelbert Effects of Long-term Smoking on Myocardial Blood Flow, Coronary Vasomotion, and Vasodilator Capacity Circulation, July 14, 1998; 98(2): 119 - 125. [Abstract] [Full Text] [PDF]
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K. Kugiyama, T. Motoyama, O. Hirashima, M. Ohgushi, H. Soejima, K. Misumi, H. Kawano, Y. Miyao, M. Yoshimura, H. Ogawa, et al. Vitamin C attenuates abnormal vasomotor reactivity in spasm coronary arteries in patients with coronary spastic angina J. Am. Coll. Cardiol., July 1, 1998; 32(1): 103 - 109. [Abstract] [Full Text] [PDF]
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S. Thorne, M. J. Mullen, P. Clarkson, A. E. Donald, and J. E. Deanfield Early endothelial dysfunction in adults at risk from atherosclerosis: different responses to L-arginine J. Am. Coll. Cardiol., July 1, 1998; 32(1): 110 - 116. [Abstract] [Full Text] [PDF]
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S. Taddei, A. Virdis, L. Ghiadoni, A. Magagna, and A. Salvetti Vitamin C Improves Endothelium-Dependent Vasodilation by Restoring Nitric Oxide Activity in Essential Hypertension Circulation, June 9, 1998; 97(22): 2222 - 2229. [Abstract] [Full Text] [PDF]
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 D. B. Cines, E. S. Pollak, C. A. Buck, J. Loscalzo, G. A. Zimmerman, R. P. McEver, J. S. Pober, T. M. Wick, B. A. Konkle, B. S. Schwartz, et al. Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders Blood, May 15, 1998; 91(10): 3527 - 3561. [Full Text] [PDF]
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W. G. Mayhan and G. M. Sharpe Nicotine impairs histamine-induced increases in macromolecular efflux: role of oxygen radicals J Appl Physiol, May 1, 1998; 84(5): 1589 - 1595. [Abstract] [Full Text] [PDF]
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S. Sugiyama, K. Kugiyama, M. Ohgushi, T. Matsumura, Y. Ota, H. Doi, N. Ogata, H. Oka, and H. Yasue Supersensitivity of atherosclerotic artery to constrictor effect of cigarette smoke extract Cardiovasc Res, May 1, 1998; 38(2): 508 - 515. [Abstract] [Full Text] [PDF]
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H. Watanabe, M. Kakihana, S. Ohtsuka, and Y. Sugishita Randomized, Double-Blind, Placebo-Controlled Study of Ascorbate on the Preventive Effect of Nitrate Tolerance in Patients With Congestive Heart Failure Circulation, March 10, 1998; 97(9): 886 - 891. [Abstract] [Full Text] [PDF]
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J. T Powell Vascular damage from smoking: disease mechanisms at the arterial wall Vascular Medicine, February 1, 1998; 3(1): 21 - 28. [Abstract] [PDF]
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 M. P. Reilly, J. A. Lawson, and G. A. FitzGerald Eicosanoids and Isoeicosanoids: Indices of Cellular Function and Oxidant Stress J. Nutr., February 1, 1998; 128(2): 434 - 434. [Abstract] [Full Text]
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 G. D. Plotnick, M. C. Corretti, and R. A. Vogel Effect of Antioxidant Vitamins on the Transient Impairment of Endothelium--Dependent Brachial Artery Vasoactivity Following a Single High-Fat Meal JAMA, November 26, 1997; 278(20): 1682 - 1686. [Abstract] [PDF]
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T. Motoyama, H. Kawano, K. Kugiyama, O. Hirashima, M. Ohgushi, M. Yoshimura, H. Ogawa, and H. Yasue Endothelium-dependent vasodilation in the brachial artery is impaired in smokers: effect of vitamin C Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1644 - H1650. [Abstract] [Full Text] [PDF]
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U. Solzbach, B. Hornig, M. Jeserich, and H. Just Vitamin C Improves Endothelial Dysfunction of Epicardial Coronary Arteries in Hypertensive Patients Circulation, September 2, 1997; 96(5): 1513 - 1519. [Abstract] [Full Text]
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H. H. Ting, F. K. Timimi, E. A. Haley, M.-A. Roddy, P. Ganz, and M. A. Creager Vitamin C Improves Endothelium-Dependent Vasodilation in Forearm Resistance Vessels of Humans With Hypercholesterolemia Circulation, June 17, 1997; 95(12): 2617 - 2622. [Abstract] [Full Text]
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M. Skatchkov, L.L. Larina, A.A. Larin, N. Fink, and E. Bassenge Urinary Nitrotyrosine Content as a Marker of Peroxynitrite-induced Tolerance to Organic Nitrates Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(2): 85 - 96. [Abstract] [PDF]
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A. Huang, J. A. Vita, R. C. Venema, and J. F. Keaney Jr. Ascorbic Acid Enhances Endothelial Nitric-oxide Synthase Activity by Increasing Intracellular Tetrahydrobiopterin J. Biol. Chem., June 2, 2000; 275(23): 17399 - 17406. [Abstract] [Full Text] [PDF]
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R. Heller, A. Unbehaun, B. Schellenberg, B. Mayer, G. Werner-Felmayer, and E. R. Werner L-Ascorbic Acid Potentiates Endothelial Nitric Oxide Synthesis via a Chemical Stabilization of Tetrahydrobiopterin J. Biol. Chem., January 5, 2001; 276(1): 40 - 47. [Abstract] [Full Text] [PDF]
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