Circulation, Vol 81, 491-497, Copyright © 1990 by American Heart Association
JA Vita, CB Treasure, EG Nabel, JM McLenachan, RD Fish, AC Yeung, VI Vekshtein, AP Selwyn and P Ganz
In animals, acetylcholine dilates normal arteries and produces
vasoconstriction in the presence of hypercholesterolemia, hypertension, or
atherosclerosis, reflecting endothelial cell dysfunction. In patients with
angiographically smooth coronary arteries, acetylcholine has been reported
to produce both vasodilation and constriction. To test the hypothesis that
the acetylcholine response relates to risk factors for coronary artery
disease, acetylcholine 10(-8) to 10(-6) M was infused into the left
anterior descending or circumflex coronary artery, and diameter changes
were assessed with quantitative angiography in 34 patients with
angiographically smooth coronary arteries. The acetylcholine response
ranged from +37% (dilation) to - 53% (constriction) at the peak
acetylcholine dose. All coronary arteries dilated in response to
nitroglycerin (26 +/- 17%), suggesting an abnormality of endothelial
function in the patients with a constrictor response to acetylcholine. By
multiple stepwise regression analysis, serum cholesterol (p less than
0.01), male gender (p less than 0.001), family history (p less than 0.05),
age (p less than 0.05), cholesterol level (p less than 0.01), and total
number of risk factors (p less than 0.0001) were independently associated
with the acetylcholine response. Thus, coronary risk factors are associated
with loss of endothelium-dependent vasodilation. The development of
vasoconstriction is likely to be an abnormality of endothelial function
that precedes atherosclerosis or an early marker of atherosclerosis not
detectable by angiography.
ARTICLES
Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
This article has been cited by other articles:
![]() |
C. J.-Y. Hou, C.-H. Tsai, C.-H. Su, Y.-J. Wu, S.-J. Chen, J.-J. Chiu, M.-S. Shiao, and H.-I Yeh Diabetes Reduces Aortic Endothelial Gap Junctions in ApoE-deficient Mice: Simvastatin Exacerbates the Reduction J. Histochem. Cytochem., August 1, 2008; 56(8): 745 - 752. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. P. Martins, C. O. Nastri, R. A. Ferriani, and F. M. Filho Brachial Artery Pulsatility Index Change 1 Minute After 5-Minute Forearm Compression: Comparison With Flow-Mediated Dilatation J. Ultrasound Med., May 1, 2008; 27(5): 693 - 699. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. L. Moens, C. J. Vrints, M. J. Claeys, J.-P. Timmermans, H. C. Champion, and D. A. Kass Mechanisms and potential therapeutic targets for folic acid in cardiovascular disease Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H1971 - H1977. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. D. Patel and R. R. Arora Review: Endothelial dysfunction: A potential tool in gender related cardiovascular disease Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 89 - 100. [Abstract] [PDF] |
||||
![]() |
M. Saglam, O. Karakaya, I. Barutcu, A. M. Esen, M. Turkmen, R. Kargin, O. Esen, N. Ozdemir, and C. Kaymaz Identifying Cardiovascular Risk Factors in a Patient Population With Coronary Artery Ectasia Angiology, January 1, 2008; 58(6): 698 - 703. [Abstract] [PDF] |
||||
![]() |
M. I. Worthley, R. S. Kanani, Y.-H. Sun, Y. Sun, D. M. Goodhart, M. J. Curtis, and T. J. Anderson Effects of tetrahydrobiopterin on coronary vascular reactivity in atherosclerotic human coronary arteries Cardiovasc Res, December 1, 2007; 76(3): 539 - 546. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. R. Duncan, S. J. Walker, V. A. Ezzat, S. B. Wheatcroft, J.-M. Li, A. M. Shah, and M. T. Kearney Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1311 - E1319. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. M. Shenouda and J. A. Vita Effects of Flavonoid-Containing Beverages and EGCG on Endothelial Function J. Am. Coll. Nutr., August 1, 2007; 26(4): 366S - 372S. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. P. Van Guilder, C. M. Westby, J. J. Greiner, B. L. Stauffer, and C. A. DeSouza Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise Hypertension, August 1, 2007; 50(2): 403 - 409. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Focardi, G. M. Dick, A. Picchi, C. Zhang, and W. M. Chilian Restoration of coronary endothelial function in obese Zucker rats by a low-carbohydrate diet Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2093 - H2099. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Barac, U. Campia, and J. A. Panza Methods for Evaluating Endothelial Function in Humans Hypertension, April 1, 2007; 49(4): 748 - 760. [Full Text] [PDF] |
||||
![]() |
A. T. Sezgin, I. Barutcu, N. Sezgin, H. Gullu, A. M. Esen, N. Acikgoz, E. Topal, and R. Ozdemir Contribution of Plasma Lipid Disturbances to Vascular Endothelial Function in Patients With Slow Coronary Flow Angiology, January 1, 2007; 57(6): 694 - 701. [Abstract] [PDF] |
||||
![]() |
A. Nohria, M. E. Grunert, Y. Rikitake, K. Noma, A. Prsic, P. Ganz, J. K. Liao, and M. A. Creager Rho Kinase Inhibition Improves Endothelial Function in Human Subjects With Coronary Artery Disease Circ. Res., December 8, 2006; 99(12): 1426 - 1432. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Taddei, D. Versari, A. Cipriano, L. Ghiadoni, F. Galetta, F. Franzoni, A. Magagna, A. Virdis, and A. Salvetti Identification of a Cytochrome P450 2C9-Derived Endothelium-Derived Hyperpolarizing Factor in Essential Hypertensive Patients J. Am. Coll. Cardiol., August 1, 2006; 48(3): 508 - 515. [Abstract] [Full Text] [PDF] |
||||
![]() |
D Fukuda, M Yoshiyama, K Shimada, H Yamashita, S Ehara, Y Nakamura, K Kamimori, A Tanaka, T Kawarabayashi, and J Yoshikawa Relation between aortic stiffness and coronary flow reserve in patients with coronary artery disease Heart, June 1, 2006; 92(6): 759 - 762. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Weiss, N. Ide, T. Abahji, L. Nill, C. Keller, and U. Hoffmann Aged Garlic Extract Improves Homocysteine-Induced Endothelial Dysfunction in Macro- and Microcirculation J. Nutr., March 1, 2006; 136(3): 750S - 754S. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Y. Chow, C. Chin, G. Dahl, and D. N. Rosenthal Anthracyclines Cause Endothelial Injury in Pediatric Cancer Patients: A Pilot Study J. Clin. Oncol., February 20, 2006; 24(6): 925 - 928. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Davis and M.-H. Zou CD40 Ligand-Dependent Tyrosine Nitration of Prostacyclin Synthase In Vivo Circulation, October 4, 2005; 112(14): 2184 - 2192. [Abstract] [Full Text] [PDF] |
||||
![]() |
U. Hagg, B. Wandt, G. Bergstrom, R. Volkmann, and L.-m. Gan Physical exercise capacity is associated with coronary and peripheral vascular function in healthy young adults Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1627 - H1634. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Neishi, S. Mochizuki, T. Miyasaka, T. Kawamoto, T. Kume, R. Sukmawan, M. Tsukiji, Y. Ogasawara, F. Kajiya, T. Akasaka, et al. Evaluation of bioavailability of nitric oxide in coronary circulation by direct measurement of plasma nitric oxide concentration PNAS, August 9, 2005; 102(32): 11456 - 11461. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. C. Newcomer, U. A. Leuenberger, C. S. Hogeman, and D. N. Proctor Heterogeneous vasodilator responses of human limbs: influence of age and habitual endurance training Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H308 - H315. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Schmidt-Lucke, L. Rossig, S. Fichtlscherer, M. Vasa, M. Britten, U. Kamper, S. Dimmeler, and A. M. Zeiher Reduced Number of Circulating Endothelial Progenitor Cells Predicts Future Cardiovascular Events: Proof of Concept for the Clinical Importance of Endogenous Vascular Repair Circulation, June 7, 2005; 111(22): 2981 - 2987. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. L. Moens, I. Goovaerts, M. J. Claeys, and C. J. Vrints Flow-Mediated Vasodilation: A Diagnostic Instrument, or an Experimental Tool? Chest, June 1, 2005; 127(6): 2254 - 2263. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Sydow, C. E Mondon, and J. P Cooke Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA Vascular Medicine, May 1, 2005; 10(2_suppl): S35 - S43. [Abstract] [PDF] |
||||
![]() |
V.-P. Valkonen, T.-P. Tuomainen, and R. Laaksonen DDAH gene and cardiovascular risk Vascular Medicine, May 1, 2005; 10(2_suppl): S45 - S48. [Abstract] [PDF] |
||||
![]() |
K. B. Vallbracht, P. L. Schwimmbeck, U. Kuhl, U. Rauch, B. Seeberg, and H.-P. Schultheiss Differential Aspects of Endothelial Function of the Coronary Microcirculation Considering Myocardial Virus Persistence, Endothelial Activation, and Myocardial Leukocyte Infiltrates Circulation, April 12, 2005; 111(14): 1784 - 1791. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Terashima, C. H. Meyer, B. G. Keeffe, E. J. Putz, E. de la Pena-Almaguer, P. C. Yang, B. S. Hu, D. G. Nishimura, and M. V. McConnell Noninvasive assessment of coronary vasodilation using magnetic resonance angiography J. Am. Coll. Cardiol., January 4, 2005; 45(1): 104 - 110. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Wiesmann, S. E. Petersen, P. M. Leeson, J. M. Francis, M. D. Robson, Q. Wang, R. Choudhury, K. M. Channon, and S. Neubauer Global impairment of brachial, carotid, and aortic vascular function in young smokers: Direct quantification by high-resolution magnetic resonance imaging J. Am. Coll. Cardiol., November 16, 2004; 44(10): 2056 - 2064. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J Green, A. Maiorana, G. O'Driscoll, and R. Taylor Effect of exercise training on endothelium-derived nitric oxide function in humans J. Physiol., November 15, 2004; 561(1): 1 - 25. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Stocker, A. Huang, E. Jeranian, J. Y. Hou, T. T. Wu, S. R. Thomas, and J. F. Keaney Jr Hypochlorous Acid Impairs Endothelium-Derived Nitric Oxide Bioactivity Through a Superoxide-Dependent Mechanism Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2028 - 2033. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Verma, C.-H. Wang, E. Lonn, F. Charbonneau, J. Buithieu, L. M. Title, M. Fung, S. Edworthy, A. C. Robertson, T. J. Anderson, et al. Cross-sectional evaluation of brachial artery flow-mediated vasodilation and C-reactive protein in healthy individuals Eur. Heart J., October 1, 2004; 25(19): 1754 - 1760. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Matsumoto, H. Takashima, N. Ohira, Y. Tarutani, Y. Yasuda, T. Yamane, S. Matsuo, and M. Horie Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin J. Am. Coll. Cardiol., July 21, 2004; 44(2): 451 - 457. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. F. Galley and N. R. Webster Physiology of the endothelium Br. J. Anaesth., July 1, 2004; 93(1): 105 - 113. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. G. Lamping, J. Wess, Y. Cui, D. W. Nuno, and F. M. Faraci Muscarinic (M) Receptors in Coronary Circulation: Gene-Targeted Mice Define the Role of M2 and M3 Receptors in Response to Acetylcholine Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1253 - 1258. [Abstract] [Full Text] [PDF] |
||||
![]() |
D.D. Waters and K.K. Khush Management of the acute coronary syndrome patient Eur. Heart J. Suppl., July 1, 2004; 6(suppl_C): C49 - C57. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Davignon and P. Ganz Role of Endothelial Dysfunction in Atherosclerosis Circulation, June 15, 2004; 109(23_suppl_1): III-27 - III-32. [Abstract] [Full Text] |
||||
![]() |
F. M. Maggi, S. Raselli, L. Grigore, L. Redaelli, S. Fantappie, and A. L. Catapano Lipoprotein Remnants and Endothelial Dysfunction in the Postprandial Phase J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2946 - 2950. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Sydow, B. Hornig, N. Arakawa, S. M Bode-Boger, D. Tsikas, T. Munuzel, and R. H Boger Endothelial dysfunction in patients with peripheral arterial disease and chronic hyperhomocysteinemia: potential role of ADMA Vascular Medicine, May 1, 2004; 9(2): 93 - 101. [Abstract] [PDF] |
||||
![]() |
G. N. Thomas, P. Chook, M. Qiao, X. S. Huang, H. C. Leong, D. S. Celermajer, and K. S. Woo Deleterious Impact of "High Normal" Glucose Levels and Other Metabolic Syndrome Components on Arterial Endothelial Function and Intima-Media Thickness in Apparently Healthy Chinese Subjects: The CATHAY Study Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 739 - 743. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. F. Harris and K. A. Matthews Interactions Between Autonomic Nervous System Activity and Endothelial Function: A Model for the Development of Cardiovascular Disease Psychosom Med, March 1, 2004; 66(2): 153 - 164. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Nitenberg, P. Valensi, R. Sachs, E. Cosson, J.-R. Attali, and I. Antony Prognostic Value of Epicardial Coronary Artery Constriction to the Cold Pressor Test in Type 2 Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Major Coronary Risk Factors Diabetes Care, January 1, 2004; 27(1): 208 - 215. [Abstract] [Full Text] [PDF] |
||||
![]() |
B.-L. Johansson, J. Sundell, K. Ekberg, C. Jonsson, M. Seppanen, O. Raitakari, M. Luotolahti, P. Nuutila, J. Wahren, and J. Knuuti C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E14 - E19. [Abstract] [Full Text] |
||||
![]() |
C. J. Pepine, J.-L. Rouleau, K. Annis, A. Ducharme, P. Ma, J. Lenis, R. Davies, U. Thadani, B. Chaitman, H. E. Haber, et al. Effects of angiotensin-converting enzyme inhibition on transient ischemia: The quinapril anti-ischemia and symptoms of angina reduction (QUASAR) trial J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2049 - 2059. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. V. Anderson Angiotensin-converting enzyme inhibitors: ischemia is not the correct measure of benefit J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2060 - 2062. [Full Text] [PDF] |
||||
![]() |
P. Ganz and J. A. Vita Testing Endothelial Vasomotor Function: Nitric Oxide, a Multipotent Molecule Circulation, October 28, 2003; 108(17): 2049 - 2053. [Full Text] [PDF] |
||||
![]() |
R. G. Schwartz, T. A. Pearson, V. G. Kalaria, M. L. Mackin, D. J. Williford, A. Awasthi, A. Shah, A. Rains, and J. J. Guido Prospective serial evaluation of myocardial perfusion and lipids during the first six months of pravastatin therapy: Coronary artery disease regression single photon emission computed tomography monitoring trial J. Am. Coll. Cardiol., August 20, 2003; 42(4): 600 - 610. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. H. Walsh, W. Bilsborough, A. Maiorana, M. Best, G. J. O'Driscoll, R. R. Taylor, and D. J. Green Exercise training improves conduit vessel function in patients with coronary artery disease J Appl Physiol, July 1, 2003; 95(1): 20 - 25. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Amar, N. Gokce, S. Morgan, M. Loukideli, T. E. Van Dyke, and J. A. Vita Periodontal Disease Is Associated With Brachial Artery Endothelial Dysfunction and Systemic Inflammation Arterioscler. Thromb. Vasc. Biol., July 1, 2003; 23(7): 1245 - 1249. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. E. Freedman High-fat diets and cardiovascular disease: Are nutritional supplements useful? J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1750 - 1752. [Full Text] [PDF] |
||||
![]() |
M. Zanetti, L. V. d'Uscio, I. Kovesdi, Z. S. Katusic, and T. O'Brien In Vivo Gene Transfer of Inducible Nitric Oxide Synthase to Carotid Arteries From Hypercholesterolemic Rabbits Stroke, May 1, 2003; 34(5): 1293 - 1298. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z S Nedeljkovic, N Gokce, and J Loscalzo Mechanisms of oxidative stress and vascular dysfunction Postgrad. Med. J., April 1, 2003; 79(930): 195 - 200. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. O. Bonetti, L. O. Lerman, and A. Lerman Endothelial Dysfunction: A Marker of Atherosclerotic Risk Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 168 - 175. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Sundell and J. Knuuti Insulin and myocardial blood flow Cardiovasc Res, February 1, 2003; 57(2): 312 - 319. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Yan, D. Kim, T. Aizawa, and B. C. Berk Functional Interplay Between Angiotensin II and Nitric Oxide: Cyclic GMP as a Key Mediator Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 26 - 36. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. L. Sutliff, S. Dikalov, D. Weiss, J. Parker, S. Raidel, A. K. Racine, R. Russ, C. P. Haase, W. R. Taylor, and W. Lewis Nucleoside reverse transcriptase inhibitors impair endothelium-dependent relaxation by increasing superoxide Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2363 - H2370. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Koenig Is measuring endothelial function a good idea for prediction of coronary heart disease complications? Eur. Heart J., November 2, 2002; 23(22): 1728 - 1730. [Full Text] [PDF] |
||||
![]() |
G. K. Sukhova, J. K. Williams, and P. Libby Statins Reduce Inflammation in Atheroma of Nonhuman Primates Independent of Effects on Serum Cholesterol Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1452 - 1458. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. G. Modena, L. Bonetti, F. Coppi, F. Bursi, and R. Rossi Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women J. Am. Coll. Cardiol., August 7, 2002; 40(3): 505 - 510. [Abstract] [Full Text] [PDF] |
||||
![]() |