JACC
HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
 QUICK SEARCH:   [advanced]


     


J Am Coll Cardiol, 1994; 24:1611-1617
© 1994 by the American College of Cardiology Foundation
This Article
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gilligan, D.
Right arrow Articles by Cannon, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gilligan, D.
Right arrow Articles by Cannon, R., 3rd

Effect of antioxidant vitamins on low density lipoprotein oxidation and impaired endothelium-dependent vasodilation in patients with hypercholesterolemia

DM Gilligan, MN Sack, V Guetta, PR Casino, AA Quyyumi, DJ Rader, JA Panza, and RO Cannon 3rd

Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.

OBJECTIVES. The aims of this study were to determine whether antioxidant vitamins could reduce the susceptibility of low density lipoprotein (LDL) to oxidation and improve endothelium-dependent vasodilator responsiveness in patients with hypercholesterolemia. BACKGROUND. Animals and humans with hypercholesterolemia have exhibited impaired endothelium-dependent vasodilation. In vitro studies suggest that oxidatively modified LDL can impair nitric oxide production. METHODS. Forearm blood flow was measured with strain gauge plethysmography and brachial artery drug infusions in 19 patients, aged 52 +/- 9 years, with hypercholesterolemia (mean +/- SD total cholesterol 283 +/- 22 mg/dl, LDL 197 +/- 31 mg/dl) and in 14 subjects, aged 48 +/- 8 years, with normal cholesterol levels (total cholesterol 169 +/- 20 mg/dl, LDL 102 +/- 25 mg/dl). Acetylcholine (7.5, 15 and 30 micrograms/min) was utilized as an endothelium-dependent vasodilator, and sodium nitroprusside (0.8, 1.6 and 3.2 micrograms/min) was used to test endothelium-independent vasodilation. Oxidative susceptibility of LDL was measured by a spectrophotometric assay of conjugated diene production after the addition of copper chloride. Hypercholesterolemic patients then received daily antioxidant vitamin supplements (beta-carotene [30 mg], ascorbic acid [vitamin C] [1,000 mg], vitamin E [800 IU]) for 1 month, with repeat measurement of both forearm blood flow responsiveness to the same agonists and LDL oxidizability. RESULTS. The maximal flow in response to acetylcholine was impaired in patients compared with that in normal subjects (9.8 +/- 7.8 vs. 15.9 +/- 8.1 ml/min per 100 ml, p = 0.03), with similar maximal flow responses to sodium nitroprusside (9.5 +/- 4.2 vs. 9.0 +/- 2.8 ml/min per 100 ml, p = 0.72). After 1 month of vitamin therapy, the onset of LDL oxidation was prolonged over baseline measurements by 71 +/- 67%, and the maximal rate of oxidation was decreased by 26 +/- 25% (both p < 0.001). However, the maximal forearm blood flow response to acetylcholine remained unchanged from baseline values (maximal flow after acetylcholine 9.0 +/- 6.2 vs. 9.8 +/- 7.8 ml/min per 100 ml, p = 0.57). This study had 80% power (alpha = 0.05) to exclude a 45% increase over baseline value in acetylcholine-stimulated flow during vitamin therapy. CONCLUSIONS. Although 1 month of administration of antioxidant vitamin supplements in hypercholesterolemic patients reduced the susceptibility of LDL to oxidation, impairment in endothelial function remained unaltered. The use of nonvitamin antioxidants or concomitant reduction in LDL levels, as well as more sensitive techniques for measuring vascular responsiveness, may be required to show a beneficial effect on endothelial vasodilator function.


This article has been cited by other articles:


Home page
Am. J. Physiol. Renal Physiol.Home page
E. Daghini, X.-Y. Zhu, D. Versari, M. D. Bentley, C. Napoli, A. Lerman, and L. O. Lerman
Antioxidant vitamins induce angiogenesis in the normal pig kidney
Am J Physiol Renal Physiol, July 1, 2007; 293(1): F371 - F381.
[Abstract] [Full Text] [PDF]


Home page
J. Appl. Physiol.Home page
P. H. McNulty, B. J. Robertson, M. A. Tulli, J. Hess, L. A. Harach, S. Scott, and L. I. Sinoway
Effect of hyperoxia and vitamin C on coronary blood flow in patients with ischemic heart disease
J Appl Physiol, May 1, 2007; 102(5): 2040 - 2045.
[Abstract] [Full Text] [PDF]


Home page
J. Appl. Physiol.Home page
C. Bell, J. M. Carson, N. W. Motte, and D. R. Seals
Ascorbic acid does not affect the age-associated reduction in maximal cardiac output and oxygen consumption in healthy adults
J Appl Physiol, March 1, 2005; 98(3): 845 - 849.
[Abstract] [Full Text] [PDF]


Home page
ANGIOLOGYHome page
B. Takase, H. Etsuda, Y. Matsushima, M. Ayaori, H. Kusano, A. Hamabe, A. Uehata, F. Ohsuzu, M. Ishihara, and A. Kurita
Effect of Chronic Oral Supplementation with Vitamins on the Endothelial Function in Chronic Smokers
Angiology, November 1, 2004; 55(6): 653 - 660.
[Abstract] [PDF]


Home page
ANGIOLOGYHome page
B. Takase, H. Etsuda, Y. Matsushima, M. Ayaori, H. Kusano, A. Hamabe, A. Uehata, F. Ohsuzu, M. Ishihara, and A. Kurita
Effect of Chronic Oral Supplementation with Vitamins on the Endothelial Function in Chronic Smokers
Angiology, November 1, 2004; 55(6): 653 - 660.
[Abstract] [PDF]


Home page
Physiol. Rev.Home page
R. Stocker and J. F. Keaney Jr.
Role of Oxidative Modifications in Atherosclerosis
Physiol Rev, October 1, 2004; 84(4): 1381 - 1478.
[Abstract] [Full Text] [PDF]


Home page
Journal of Renin-Angiotensin-Aldosterone SystemHome page
J. S. Sim, C. Farquharson, and A. D Struthers
Tonic levels of angiotensin II reduce tonic levels of vascular nitric oxide even in salt-replete man
Journal of Renin-Angiotensin-Aldosterone System, June 1, 2004; 5(2): 84 - 88.
[Abstract] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
I. Eskurza, K. D. Monahan, J. A. Robinson, and D. R. Seals
Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men
Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1528 - H1534.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
S. Kinlay, D. Behrendt, J. C. Fang, D. Delagrange, J. Morrow, J. L. Witztum, N. Rifai, A. P. Selwyn, M. A. Creager, and P. Ganz
long-term effect of combined vitamins e and c on coronary and peripheral endothelial function
J. Am. Coll. Cardiol., February 18, 2004; 43(4): 629 - 634.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
M. E. Widlansky, N. Gokce, J. F. Keaney Jr, and J. A. Vita
The clinical implications of endothelial dysfunction
J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1149 - 1160.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
N. Singh, J. Graves, P. D Taylor, R. J MacAllister, and D. R.J Singer
Effects of a 'healthy' diet and of acute and long-term vitamin C on vascular function in healthy older subjects
Cardiovasc Res, October 1, 2002; 56(1): 118 - 125.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
J. H. Stein, C. M. Carlsson, K. Papcke-Benson, S. E. Aeschlimann, A. Bodemer, M. Carnes, and P. E. McBride
The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia
J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1806 - 1813.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
J. M. STULAK, A. LERMAN, M. R. PORCEL, J. A. CACCITOLO, J. C. ROMERO, H. V. SCHAFF, C. NAPOLI, and L. O. LERMAN
Renal Vascular Function in Hypercholesterolemia Is Preserved by Chronic Antioxidant Supplementation
J. Am. Soc. Nephrol., September 1, 2001; 12(9): 1882 - 1891.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
W. F. Penny, O. Ben-Yehuda, K. Kuroe, J. Long, A. Bond, V. Bhargava, J. F. Peterson, M. McDaniel, J. Juliano, J. L. Witztum, et al.
Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein
J. Am. Coll. Cardiol., March 1, 2001; 37(3): 766 - 774.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
M. Rodriguez-Porcel, A. Lerman, P. J. M. Best, J. D. Krier, C. Napoli, and L. O. Lerman
Hypercholesterolemia impairs myocardial perfusion and permeability: role of oxidative stress and endogenous scavenging activity
J. Am. Coll. Cardiol., February 1, 2001; 37(2): 608 - 615.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
A. C. Carr, B.-Z. Zhu, and B. Frei
Potential Antiatherogenic Mechanisms of Ascorbate (Vitamin C) and {alpha}-Tocopherol (Vitamin E)
Circ. Res., September 1, 2000; 87(5): 349 - 354.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
D. Tomasian, J. F. Keaney Jr., and J. A. Vita
Antioxidants and the bioactivity of endothelium-derived nitric oxide
Cardiovasc Res, August 18, 2000; 47(3): 426 - 435.
[Full Text] [PDF]


Home page
J Am Coll CardiolHome page
R. A. P. Skyrme-Jones, R. C. O'Brien, K. L. Berry, and I. T. Meredith
Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study
J. Am. Coll. Cardiol., July 1, 2000; 36(1): 94 - 102.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
O. T. Raitakari, M. R. Adams, R. J. McCredie, K. A. Griffiths, R. Stocker, and D. S. Celermajer
Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect
J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1616 - 1621.
[Abstract] [Full Text] [PDF]


Home page
J. Gerontol. A Biol. Sci. Med. Sci.Home page
L. R. Peterson, M. Courtois, L. F. Peterson, M. R. Peterson, V. G. Dávila-Román, R. J. Spina, and B. Barzilai
Estrogen Increases Hyperemic Microvascular Blood Flow Velocity in Postmenopausal Women
J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2000; 55(3): 174M - 179.
[Abstract] [Full Text]


Home page
J Am Coll CardiolHome page
T. Neunteufl, U. Priglinger, S. Heher, M. Zehetgruber, G. Soregi, S. Lehr, K. Huber, G. Maurer, F. Weidinger, and K. Kostner
Effects of vitamin E on chronic and acute endothelial dysfunction in smokers
J. Am. Coll. Cardiol., February 1, 2000; 35(2): 277 - 283.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
R. A. P. Skyrme-Jones, R. C. O'Brien, M. Luo, and I. T. Meredith
Endothelial vasodilator function is related to low-density lipoprotein particle size and low-density lipoprotein vitamin E content in type 1 diabetes
J. Am. Coll. Cardiol., February 1, 2000; 35(2): 292 - 299.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
J. M. Mostaza, M. V. Gomez, F. Gallardo, M. L. Salazar, R. Martin-Jadraque, L. Plaza-Celemin, I. Gonzalez-Maqueda, and L. Martin-Jadraque
Cholesterol reduction improves myocardial perfusion abnormalities in patients with coronary artery disease and average cholesterol levels
J. Am. Coll. Cardiol., January 1, 2000; 35(1): 76 - 82.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
C. Palombo, V. Lubrano, and T. Sampietro
Oxidative stress, F2-isoprostanes and endothelial dysfunction in hypercholesterolemia
Cardiovasc Res, December 1, 1999; 44(3): 474 - 476.
[Full Text] [PDF]


Home page
J Am Coll CardiolHome page
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]


Home page
Cardiovasc ResHome page
G. Kojda and D. Harrison
Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure
Cardiovasc Res, August 15, 1999; 43(3): 652 - 671.
[Full Text] [PDF]


Home page
Cardiovasc ResHome page
A. M Dart and J. P.F Chin-Dusting
Lipids and the endothelium
Cardiovasc Res, August 1, 1999; 43(2): 308 - 322.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
N. Gokce, J. F. Keaney Jr, B. Frei, M. Holbrook, M. Olesiak, B. J. Zachariah, C. Leeuwenburgh, J. W. Heinecke, and J. A. Vita
Long-Term Ascorbic Acid Administration Reverses Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease
Circulation, June 29, 1999; 99(25): 3234 - 3240.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Clin. Nutr.Home page
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]


Home page
FASEB J.Home page
J. F. KEANEY JR., D. I. SIMON, and J. E. FREEDMAN
Vitamin E and vascular homeostasis: implications for atherosclerosis
FASEB J, June 1, 1999; 13(9): 965 - 975.
[Abstract] [Full Text]


Home page
J Am Coll CardiolHome page
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]


Home page
J Am Coll CardiolHome page
T. Heitzer, S. Y. Herttuala, E. Wild, J. Luoma, and H. Drexler
Effect of vitamin E on endothelial vasodilator function in patients with hypercholesterolemia, chronic smoking or both
J. Am. Coll. Cardiol., February 1, 1999; 33(2): 499 - 505.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
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]


Home page
CirculationHome page
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]


Home page
CirculationHome page
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]


Home page
CirculationHome page
V. Guetta and R. O. Cannon III
Cardiovascular Effects of Estrogen and Lipid-Lowering Therapies in Postmenopausal Women
Circulation, May 15, 1996; 93(10): 1928 - 1937.
[Full Text]


Home page
CirculationHome page
G. N. Levine, B. Frei, S. N. Koulouris, M. D. Gerhard, J. F. Keaney Jr, and J. A. Vita
Ascorbic Acid Reverses Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease
Circulation, March 15, 1996; 93(6): 1107 - 1113.
[Abstract] [Full Text]




HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
Copyright © 1994 by the American College of Cardiology Foundation.