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(Circulation. 1996;93:1107-1113.)
© 1996 American Heart Association, Inc.
Articles |
Ascorbic Acid Reverses Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease
From the Evans Memorial Department of Medicine and the Whitaker Cardiovascular Institute, Boston University Medical Center (G.N.L., B.F., S.N.K., J.F.K., J.A.V.), and the Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School (M.D.G.), Boston, Mass.
Background In the setting of atherosclerosis, endothelial vasomotor function is abnormal. Increased oxidative stress has been implicated as one potential mechanism for this observation. We therefore hypothesized that an antioxidant, ascorbic acid, would improve endothelium-dependent arterial dilation in patients with coronary artery disease.
Methods and Results Brachial artery endothelium-dependent dilation in response to hyperemia was assessed by high-resolution vascular ultrasound before and 2 hours after oral administration of either 2 g ascorbic acid or placebo in a total of 46 patients with documented coronary artery disease. Plasma ascorbic acid concentration increased 2.5-fold 2 hours after treatment (46±8 to 114±11 µmol/L, P=.001). In the prospectively defined group of patients with an abnormal baseline response (<5% dilation), ascorbic acid produced marked improvement in dilation (2.0±0.6% to 9.7±2.0%), whereas placebo had no effect (1.1±1.5% to 1.7±1.5%, P=.003 for ascorbic acid versus placebo). Ascorbic acid had no effect on hyperemic flow or arterial dilation to sublingual nitroglycerin.
Conclusions Ascorbic acid reverses endothelial vasomotor dysfunction in the brachial circulation of patients with coronary artery disease. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in patients with atherosclerosis and that endothelial dysfunction may respond to antioxidant therapy.
Key Words: antioxidants • endothelium • coronary disease
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M. Jeserich, T. Schindler, M. Olschewski, M. Unmussig, H. Just, and U. Solzbach Vitamin C improves endothelial function of epicardial coronary arteries in patients with hypercholesterolaemia or essential hypertension--assessed by cold pressor testing Eur. Heart J., November 2, 1999; 20(22): 1676 - 1680. [Abstract] [PDF]
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K. K. Koh, A. Blum, L. Hathaway, R. Mincemoyer, G. Csako, M. A. Waclawiw, J. A. Panza, and R. O. Cannon III Vascular Effects of Estrogen and Vitamin E Therapies in Postmenopausal Women Circulation, November 2, 1999; 100(18): 1851 - 1857. [Abstract] [Full Text] [PDF]
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R. C. M. Siow, J. P. Richards, K. C. Pedley, D. S. Leake, and G. E. Mann Vitamin C Protects Human Vascular Smooth Muscle Cells Against Apoptosis Induced by Moderately Oxidized LDL Containing High Levels of Lipid Hydroperoxides Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2387 - 2394. [Abstract] [Full Text] [PDF]
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P. M. Kanani, C. A. Sinkey, R. L. Browning, M. Allaman, H. R. Knapp, and W. G. Haynes Role of Oxidant Stress in Endothelial Dysfunction Produced by Experimental Hyperhomocyst(e)inemia in Humans Circulation, September 14, 1999; 100(11): 1161 - 1168. [Abstract] [Full Text] [PDF]
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J. H. Stein, J. G. Keevil, D. A. Wiebe, S. Aeschlimann, and J. D. Folts Purple Grape Juice Improves Endothelial Function and Reduces the Susceptibility of LDL Cholesterol to Oxidation in Patients With Coronary Artery Disease Circulation, September 7, 1999; 100(10): 1050 - 1055. [Abstract] [Full Text] [PDF]
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T. J. Anderson Assessment and treatment of endothelial dysfunction in humans J. Am. Coll. Cardiol., September 1, 1999; 34(3): 631 - 638. [Full Text] [PDF]
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P. Voci, G. Testa, G. Plaustro, and Q. Caretta Coronary Doppler intensity changes during handgrip: a new method to detect coronary vasomotor tone in coronary artery disease J. Am. Coll. Cardiol., August 1, 1999; 34(2): 428 - 434. [Abstract] [Full Text] [PDF]
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S. Kinlay, J. C. Fang, H. Hikita, I. Ho, D. M. Delagrange, B. Frei, J. H. Suh, M. Gerhard, M. A. Creager, A. P. Selwyn, et al. Plasma {alpha}-Tocopherol and Coronary Endothelium-Dependent Vasodilator Function Circulation, July 20, 1999; 100(3): 219 - 221. [Abstract] [Full Text] [PDF]
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 S. Ramasamy, G. R. Drummond, J. Ahn, M. Storek, J. Pohl, S. Parthasarathy, and D. G. Harrison Modulation of Expression of Endothelial Nitric Oxide Synthase by Nordihydroguaiaretic Acid, a Phenolic Antioxidant in Cultured Endothelial Cells Mol. Pharmacol., July 1, 1999; 56(1): 116 - 123. [Abstract] [Full Text]
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A. C Carr and B. Frei Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans Am. J. Clinical Nutrition, June 1, 1999; 69(6): 1086 - 1107. [Abstract] [Full Text] [PDF]
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 S. Lawson Evidence exists for some advertising claims made on the internet BMJ, May 29, 1999; 318(7196): 1484 - 1484. [Full Text]
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J. P Cooke The 1998 Nobel prize in Medicine: clinical implications for 1999 and beyond Vascular Medicine, May 1, 1999; 4(2): 57 - 60. [PDF]
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G. O'Driscoll, D. Green, A. Maiorana, K. Stanton, F. Colreavy, and R. Taylor Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1506 - 1511. [Abstract] [Full Text] [PDF]
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K. Kugiyama, T. Motoyama, H. Doi, H. Kawano, N. Hirai, H. Soejima, Y. Miyao, K. Takazoe, Y. Moriyama, Y. Mizuno, et al. Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1512 - 1518. [Abstract] [Full Text] [PDF]
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 R. Heller, F. Munscher-Paulig, R. Grabner, and U. Till L-Ascorbic Acid Potentiates Nitric Oxide Synthesis in Endothelial Cells J. Biol. Chem., March 19, 1999; 274(12): 8254 - 8260. [Abstract] [Full Text] [PDF]
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M. L. Muiesan, M. Salvetti, C. Monteduro, D. Rizzoni, R. Zulli, C. Corbellini, C. Brun, and E. Agabiti-Rosei Effect of Treatment on Flow-Dependent Vasodilation of the Brachial Artery in Essential Hypertension Hypertension, January 1, 1999; 33(1): 575 - 580. [Abstract] [Full Text] [PDF]
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F. Perticone, R. Ceravolo, R. Maio, G. Ventura, S. Iacopino, G. Cuda, P. Mastroroberto, M. Chello, and P. L. Mattioli Calcium antagonist isradipine improves abnormal endothelium-dependent vasodilation in never treated hypertensive patients Cardiovasc Res, January 1, 1999; 41(1): 299 - 306. [Abstract] [Full Text] [PDF]
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P. R. A. Caramori, A. G. Adelman, E. R. Azevedo, G. E. Newton, A. B. Parker, and J. D. Parker Therapy with nitroglycerin increases coronary vasoconstriction in response to acetylcholine J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1969 - 1974. [Abstract] [Full Text] [PDF]
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 G. Lizard, S. Gueldry, O. Sordet, S. Monier, A. Athias, C. Miguet, G. Bessede, S. Lemaire, E. Solary, and P. Gambert Glutathione is implied in the control of 7-ketocholesterol-induced apoptosis, which is associated with radical oxygen species production FASEB J, December 1, 1998; 12(15): 1651 - 1663. [Abstract] [Full Text]
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T. Motoyama, H. Kawano, K. Kugiyama, O. Hirashima, M. Ohgushi, R. Tsunoda, Y. Moriyama, Y. Miyao, M. Yoshimura, H. Ogawa, et al. Vitamin E administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina J. Am. Coll. Cardiol., November 15, 1998; 32(6): 1672 - 1679. [Abstract] [Full Text] [PDF]
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R. C. M. Siow, H. Sato, D. S. Leake, J. D. Pearson, S. Bannai, and G. E. Mann Vitamin C Protects Human Arterial Smooth Muscle Cells Against Atherogenic Lipoproteins : Effects of Antioxidant Vitamins C and E on Oxidized LDL–Induced Adaptive Increases in Cystine Transport and Glutathione Arterioscler Thromb Vasc Biol, October 1, 1998; 18(10): 1662 - 1670. [Abstract] [Full Text] [PDF]
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T. Neunteufl, K. Kostner, R. Katzenschlager, M. Zehetgruber, G. Maurer, and F. Weidinger Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men J. Am. Coll. Cardiol., September 1, 1998; 32(3): 711 - 716. [Abstract] [Full Text] [PDF]
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 B. W. Mays, T. Ripple, M. T. Eginton, G. R. Seabrook, R. A. Cambria, J. B. Towne, and J. A. Freischlag Smoking Cessation Reverses Arterial Endothelium-Dependent Relaxation Injury Vascular and Endovascular Surgery, September 1, 1998; 32(5): 407 - 413. [Abstract] [PDF]
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T. W. Hein and L. Kuo LDLs Impair Vasomotor Function of the Coronary Microcirculation : Role of Superoxide Anions Circ. Res., August 24, 1998; 83(4): 404 - 414. [Abstract] [Full Text] [PDF]
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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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K. Bhagat Endothelial function and myocardial infarction Cardiovasc Res, August 1, 1998; 39(2): 312 - 317. [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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K. Kugiyama, M. Ohgushi, T. Motoyama, O. Hirashima, H. Soejima, K. Misumi, M. Yoshimura, H. Ogawa, S. Sugiyama, and H. Yasue Intracoronary Infusion of Reduced Glutathione Improves Endothelial Vasomotor Response to Acetylcholine in Human Coronary Circulation Circulation, June 16, 1998; 97(23): 2299 - 2301. [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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