From the Cardiology Branch, National Heart, Lung, and Blood Institute,
Bethesda, Md.
Background—The beneficial effects of
aspirin in atherosclerosis are generally attributed to
its antiplatelet activities, but its influence on
endothelial function remains uncertain. We hypothesized
that a cyclooxygenase-dependent constricting factor
contributes to the endothelial dysfunction in
atherosclerosis and that its action can be reversed
by aspirin.
Methods and Results—In 14 patients with coronary
atherosclerosis and 5 with risk factors, we tested
femoral vascular endothelial function with
acetylcholine and substance P and
endothelium-independent function with sodium
nitroprusside before and after intravenous aspirin. Drugs
were infused into the femoral artery, and Doppler flow velocity was
measured. Acetylcholine-induced but not substance P–or sodium
nitroprusside–induced vasodilation was lower in patients with
atherosclerosis than in those with only risk factors.
Aspirin had no baseline effect but improved acetylcholine-mediated
vasodilation only in patients with atherosclerosis; at
the peak dose, acetylcholine-mediated femoral vascular resistance index
was 19±5%, P=.002 lower. There was a correlation
between the baseline response to acetylcholine and the magnitude of
improvement with aspirin (r=.5, P=.05).
Thus, patients with a depressed response to acetylcholine had greater
improvement with aspirin, and vice versa. The presence of
atherosclerosis was an independent determinant of
improvement with aspirin. Aspirin had no effect on the responses to
either substance P or sodium nitroprusside.
Conclusions—Cyclooxygenase-dependent,
endothelium-derived vasoconstrictor release modulates
acetylcholine-induced peripheral vasodilation in patients
with atherosclerosis. Improvement of
endothelial dysfunction with aspirin may improve
vasodilation, reduce thrombosis, and inhibit progression of
atherosclerosis and provides a
pathophysiological basis for the beneficial effects
of aspirin in atherosclerosis.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Aspirin Improves Endothelial Dysfunction in Atherosclerosis
Key Words: endothelium-derived factors • aspirin • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  J. D. Snoep, M. M.C. Hovens, S. M. Pasha, M. Frolich, H. Pijl, J. T. Tamsma, and M. V. Huisman Time-Dependent Effects of Low-Dose Aspirin on Plasma Renin Activity, Aldosterone, Cortisol, and Catecholamines Hypertension, November 1, 2009; 54(5): 1136 - 1142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. T. Newsome, M. A. Kutcher, and R. L. Royster Coronary Artery Stents: Part I. Evolution of Percutaneous Coronary Intervention Anesth. Analg., August 1, 2008; 107(2): 552 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hirao, K. Kondo, K. Takeuchi, N. Inui, K. Umemura, K. Ohashi, and H. Watanabe Cyclooxygenase-dependent vasoconstricting factor(s) in remodelled rat femoral arteries Cardiovasc Res, July 1, 2008; 79(1): 161 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Patrono, C. Baigent, J. Hirsh, and G. Roth Antiplatelet Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 199S - 233S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Maree and D. J. Fitzgerald Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease Circulation, April 24, 2007; 115(16): 2196 - 2207. [Full Text] [PDF]
|
|
|
|
 |
|
 R. P Raghavan, D. W Laight, K. M Shaw, and M. H Cummings Review: Aspirin and diabetes The British Journal of Diabetes & Vascular Disease, March 1, 2006; 6(2): 74 - 82. [Abstract] [PDF]
|
|
|
|
 |
|
 P. C. Williams, M. J. Coffey, B. Coles, S. Sanchez, J. D. Morrow, J. R. Cockcroft, M. J. Lewis, and V. B. O'Donnell In vivo aspirin supplementation inhibits nitric oxide consumption by human platelets Blood, October 15, 2005; 106(8): 2737 - 2743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Forman, M. J. Stampfer, and G. C. Curhan Non-Narcotic Analgesic Dose and Risk of Incident Hypertension in US Women Hypertension, September 1, 2005; 46(3): 500 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sanderson, J. Emery, T. Baglin, and A.-L. Kinmonth Narrative Review: Aspirin Resistance and Its Clinical Implications Ann Intern Med, March 1, 2005; 142(5): 370 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Morgan, L. J. Dixon, C. G. Hanratty, S. M.T. Hughes, W. J. Leahey, K. P. Rooney, G. D. Johnston, and G. E. McVeigh Impaired endothelium-dependent and -independent vasodilation in elderly patients with chronic heart failure Eur J Heart Fail, December 1, 2004; 6(7): 901 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cattaneo Aspirin and Clopidogrel: Efficacy, Safety, and the Issue of Drug Resistance Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 1980 - 1987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Patrono, B. Coller, G. A. FitzGerald, J. Hirsh, and G. Roth Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 234S - 264S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bogaty, J. M. Brophy, M. Noel, L. Boyer, S. Simard, F. Bertrand, and G. R. Dagenais Impact of Prolonged Cyclooxygenase-2 Inhibition on Inflammatory Markers and Endothelial Function in Patients With Ischemic Heart Disease and Raised C-Reactive Protein: A Randomized Placebo-Controlled Study Circulation, August 24, 2004; 110(8): 934 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Cohn, A. A. Quyyumi, N. K. Hollenberg, and K. A. Jamerson Surrogate Markers for Cardiovascular Disease: Functional Markers Circulation, June 29, 2004; 109(25_suppl_1): IV-31 - IV-46. [Full Text] [PDF]
|
|
|
|
 |
|
 D. J.H. McCabe, P. Harrison, S. J. Machin, H. Watt, M. M. Brown, and M. J. Alberts Measurement of the Antiplatelet Effects of Aspirin in Cerebrovascular Disease * Response Stroke, June 1, 2004; 35(6): e146 - e147. [Full Text] [PDF]
|
|
|
|
 |
|
 W. Dai and R. A. Kloner Relationship Between Cyclooxygenase-2 Inhibition and Thrombogenesis Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2004; 9(1): 51 - 59. [Abstract] [PDF]
|
|
|
|
 |
|
 A. C. Betik, V. B. Luckham, and R. L. Hughson Flow-mediated dilation in human brachial artery after different circulatory occlusion conditions Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H442 - H448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Title, K. Giddens, M. M. McInerney, M. J. McQueen, and B. A. Nassar Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction and inflammatory markers in patients with coronary artery disease J. Am. Coll. Cardiol., November 19, 2003; 42(10): 1747 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Widlansky, D. T. Price, N. Gokce, R. T. Eberhardt, S. J. Duffy, M. Holbrook, C. Maxwell, J. Palmisano, J. F. Keaney Jr, J. D. Morrow, et al. Short- and Long-Term COX-2 Inhibition Reverses Endothelial Dysfunction in Patients With Hypertension Hypertension, September 1, 2003; 42(3): 310 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Grosser and H. Schroder Aspirin Protects Endothelial Cells From Oxidant Damage Via the Nitric Oxide-cGMP Pathway Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1345 - 1351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. V. Targonski, P. O. Bonetti, G. M. Pumper, S. T. Higano, D. R. Holmes Jr, and A. Lerman Coronary Endothelial Dysfunction Is Associated With an Increased Risk of Cerebrovascular Events Circulation, June 10, 2003; 107(22): 2805 - 2809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Belhassen, G. Pelle, J.-L. Dubois-Rande, and S. Adnot Improved endothelial function by the thromboxane a2 receptor antagonist s 18886 in patients with coronary artery disease treated with aspirin J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1198 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-q. Zhu, R. E Sievers, A. E. Browne, R. J Lee, K. Chatterjee, W. Grossman, J. S Karliner, and W. W Parmley Comparative effects of aspirin with ACE inhibitor or angiotensin receptor blocker on myocardial infarction and vascular function Journal of Renin-Angiotensin-Aldosterone System, March 1, 2003; 4(1): 31 - 37. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Hassan, B. J. Hunt, M. O'Sullivan, K. Parmar, J. M. Bamford, D. Briley, M. M. Brown, D. J. Thomas, and H. S. Markus Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis Brain, February 1, 2003; 126(2): 424 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Chenevard, D. Hurlimann, M. Bechir, F. Enseleit, L. Spieker, M. Hermann, W. Riesen, S. Gay, R. E. Gay, M. Neidhart, et al. Selective COX-2 Inhibition Improves Endothelial Function in Coronary Artery Disease Circulation, January 28, 2003; 107(3): 405 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ooi, W. S. Colucci, and M. M. Givertz Endothelin Mediates Increased Pulmonary Vascular Tone in Patients With Heart Failure: Demonstration by Direct Intrapulmonary Infusion of Sitaxsentan Circulation, September 24, 2002; 106(13): 1618 - 1621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Mangiafico, L. S. Malatino, T. Attina, R. Messina, and C. E. Fiore Exaggerated Endothelin Release in Response to Acute Mental Stress in Patients with Intermittent Claudication Angiology, July 1, 2002; 53(4): 383 - 390. [Abstract] [PDF]
|
|
|
|
|
|
R. K. Kharbanda, B. Walton, M. Allen, N. Klein, A. D. Hingorani, R. J. MacAllister, and P. Vallance Prevention of Inflammation-Induced Endothelial Dysfunction: A Novel Vasculo-Protective Action of Aspirin Circulation, June 4, 2002; 105(22): 2600 - 2604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Whigham, A. Higbee, D. E. Bjorling, Y. Park, M. W. Pariza, and M. E. Cook Decreased antigen-induced eicosanoid release in conjugated linoleic acid-fed guinea pigs Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1104 - R1112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Berghoff, M. Kathpal, S. Kilo, M. J. Hilz, and R. Freeman Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation J Appl Physiol, February 1, 2002; 92(2): 780 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Lincoln, N. Dey, and H. Sellak Signal Transduction in Smooth Muscle: Invited Review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression J Appl Physiol, September 1, 2001; 91(3): 1421 - 1430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Voisard, R. Fischer, M. O{beta}wald, S. Voglic, R. Baur, M. Susa, W. Koenig, and V. Hombach Aspirin (5 mmol/L) Inhibits Leukocyte Attack and Triggered Reactive Cell Proliferation in a 3D Human Coronary In Vitro Model Circulation, March 27, 2001; 103(12): 1688 - 1694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wu, M. G. Hayek, and S. N. Meydani Vitamin E and Macrophage Cyclooxygenase Regulation in the Aged J. Nutr., February 1, 2001; 131(2): 382S - 388. [Abstract] [Full Text]
|
|
|
|
|
|
N. P. Andrews, A. Prasad, and A. A. Quyyumi N-acetylcysteine improves coronary and peripheral vascular function J. Am. Coll. Cardiol., January 1, 2001; 37(1): 117 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Patrono, B. Coller, J. E. Dalen, G. A. FitzGerald, V. Fuster, M. Gent, J. Hirsh, and G. Roth Platelet-Active Drugs : The Relationships Among Dose, Effectiveness, and Side Effects Chest, January 1, 2001; 119 (2009): 39S - 63S. [Full Text] [PDF]
|
|
|
|
|
|
P. Liuba, P. Karnani, E. Pesonen, I. Paakkari, A. Forslid, L. Johansson, K. Persson, T. Wadstrom, and R. Laurini Endothelial Dysfunction After Repeated Chlamydia pneumoniae Infection in Apolipoprotein E-Knockout Mice Circulation, August 29, 2000; 102(9): 1039 - 1044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Prasad, T. Tupas-Habib, W. H. Schenke, R. Mincemoyer, J. A. Panza, M. A. Waclawin, S. Ellahham, and A. A. Quyyumi Acute and Chronic Angiotensin-1 Receptor Antagonism Reverses Endothelial Dysfunction in Atherosclerosis Circulation, May 23, 2000; 101(20): 2349 - 2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. Awtry and J. Loscalzo Aspirin Circulation, March 14, 2000; 101(10): 1206 - 1218. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vigili de Kreutzenberg, C. Crepaldi, S. Marchetto, L. Calò, A. Tiengo, S. Del Prato, and A. Avogaro Plasma Free Fatty Acids and Endothelium-Dependent Vasodilation: Effect of Chain-Length and Cyclooxygenase Inhibition J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 793 - 798. [Abstract] [Full Text]
|
|
|
|
|
|
T. Osanai, N. Fujita, N. Fujiwara, T. Nakano, K. Takahashi, W. Guan, and K. Okumura Cross talk of shear-induced production of prostacyclin and nitric oxide in endothelial cells Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H233 - H238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Yang, L. Powell-Braxton, A. K. Ogaoawara, N. Dybdal, S. Bunting, O. Ohneda, and H. Jin Hypertension and Endothelial Dysfunction in Apolipoprotein E Knockout Mice Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2762 - 2768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Schonbeck, G. K. Sukhova, P. Graber, S. Coulter, and P. Libby Augmented Expression of Cyclooxygenase-2 in Human Atherosclerotic Lesions Am. J. Pathol., October 1, 1999; 155(4): 1281 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Prasad, N. P. Andrews, F. A. Padder, M. Husain, and A. A. Quyyumi Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability J. Am. Coll. Cardiol., August 1, 1999; 34(2): 507 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Zou, M. Leist, and V. Ullrich Selective Nitration of Prostacyclin Synthase and Defective Vasorelaxation in Atherosclerotic Bovine Coronary Arteries Am. J. Pathol., May 1, 1999; 154(5): 1359 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Dakak, S. Husain, D. Mulcahy, N. P. Andrews, J. A. Panza, M. Waclawiw, W. Schenke, and A. A. Quyyumi Contribution of Nitric Oxide to Reactive Hyperemia : Impact of Endothelial Dysfunction Hypertension, July 1, 1998; 32(1): 9 - 15. [Abstract] [Full Text] [PDF]
|
|