Circulation, Vol 83, 391-401, Copyright © 1991 by American Heart Association
AM Zeiher, H Drexler, H Wollschlager and H Just
The endothelium plays a critical role in the control of vasomotor tone by
the release of vasoactive substances. Because endothelial injury or
dysfunction is considered important very early in atherogenesis, we
hypothesized that abnormal endothelial function precedes the angiographic
detection of coronary atherosclerosis in the human coronary circulation.
The coronary vasomotor responses to three different endothelium-mediated
stimuli (intracoronary infusion of acetylcholine 10(-8) to 10(-6) M,
increase in blood flow to induce flow- dependent dilation, and sympathetic
stimulation by cold pressor testing) were assessed by quantitative
angiography and subselective intracoronary Doppler flow velocity
measurements within the left anterior descending coronary artery in 38
patients. All three stimuli elicited epicardial artery dilation in all 11
patients with smooth coronary arteries and absence of risk factors for
coronary artery disease (group 1). All nine patients with smooth coronary
arteries but with hypercholesterolemia (group 2) demonstrated a selective
impairment in endothelial function with vasoconstriction (35 +/- 12.7%
decrease in mean luminal area) in response to acetylcholine but showed a
preserved flow-dependent dilation (15.5 +/- 4.4% increase in mean luminal
area) and vasodilation in response to cold pressor testing (14.2 +/- 4.6%
increase in mean luminal area). In all nine patients with an
angiographically defined smooth coronary artery segment but with evidence
of atherosclerosis elsewhere in the coronary system (group 3), both
acetylcholine and cold pressor testing induced vasoconstriction (26.2 +/-
8.7% and 18.7 +/- 7.9% decrease in mean luminal area, respectively),
whereas flow-dependent dilation was preserved (20.4 +/- 8.7% increase in
mean luminal area). In the nine patients with angiographic evidence of wall
irregularities (group 4), flow-dependent dilation was also abolished and
vasoconstriction occurred in response to acetylcholine and cold pressor
testing (34.5 +/- 10.7% and 19.9 +/- 6.3% decrease in mean luminal area,
respectively). All coronary artery segments dilated in response to
nitroglycerin, suggesting preserved function of vascular smooth muscle.
Despite similar reductions in coronary vascular resistance in response to
the smooth muscle relaxant papaverin, patients with hypercholesterolemia
demonstrated a selective impairment of vasodilation of the resistance
vasculature in response to acetylcholine (p less than 0.05 versus groups 1,
3, and 4). Thus, there is a progressive impairment of endothelial
vasoactive functioning in coronary arteries of patients with different
early stages of atherosclerosis, beginning with a selective endothelial
dysfunction in angiographically defined normal arteries in patients with
hypercholesterolemia and progressively worsening to a complete loss of
endothelium-mediated vasodilation in angiographically defined
atherosclerotic coronary arteries.(ABSTRACT TRUNCATED AT 400 WORDS)
ARTICLES
Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis
Department of Cardiology, University of Freiburg, FRG.
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S. Kinlay, D. Behrendt, M. Wainstein, J. Beltrame, J. C. Fang, M. A. Creager, A. P. Selwyn, and P. Ganz Role of Endothelin-1 in the Active Constriction of Human Atherosclerotic Coronary Arteries Circulation, September 4, 2001; 104(10): 1114 - 1118. [Abstract] [Full Text] [PDF]
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E. Lutgens, E. D. de Muinck, S. Heeneman, and M. J.A.P. Daemen Compensatory Enlargement and Stenosis Develop in ApoE-/- and ApoE*3-Leiden Transgenic Mice Arterioscler Thromb Vasc Biol, August 1, 2001; 21(8): 1359 - 1365. [Abstract] [Full Text] [PDF]
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M. Hernandez-Pampaloni, F. Y.J. Keng, T. Kudo, J. S. Sayre, and H. R. Schelbert Abnormal Longitudinal, Base-to-Apex Myocardial Perfusion Gradient by Quantitative Blood Flow Measurements in Patients With Coronary Risk Factors Circulation, July 31, 2001; 104(5): 527 - 532. [Abstract] [Full Text] [PDF]
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K. L. Goh, A. C. Shore, M. Quinn, and J. E. Tooke Impaired Microvascular Vasodilatory Function in 3-Month-Old Infants of Low Birth Weight Diabetes Care, June 1, 2001; 24(6): 1102 - 1107. [Abstract] [Full Text]
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D. E. Newby, A. L. McLeod, N. G. Uren, L. Flint, C. A. Ludlam, D. J. Webb, K. A. A. Fox, and N. A. Boon Impaired Coronary Tissue Plasminogen Activator Release Is Associated With Coronary Atherosclerosis and Cigarette Smoking : Direct Link Between Endothelial Dysfunction and Atherothrombosis Circulation, April 17, 2001; 103(15): 1936 - 1941. [Abstract] [Full Text] [PDF]
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W. J. Kop, D. S. Krantz, R. H. Howell, M. A. Ferguson, V. Papademetriou, D. Lu, J. J. Popma, J. F. Quigley, M. Vernalis, and J. S. Gottdiener Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: relationship with hemodynamic stress responses J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1359 - 1366. [Abstract] [Full Text] [PDF]
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C. Rodriguez, J. Martinez-Gonzalez, S. Sanchez-Gomez, and L. Badimon LDL Downregulates CYP51 in Porcine Vascular Endothelial Cells and in the Arterial Wall Through a Sterol Regulatory Element Binding Protein-2-Dependent Mechanism Circ. Res., February 16, 2001; 88(3): 268 - 274. [Abstract] [Full Text] [PDF]
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D Pagano, F Fath-Ordoubadi, K J Beatt, J N Townend, R S Bonser, and P G Camici Effects of coronary revascularisation on myocardial blood flow and coronary vasodilator reserve in hibernating myocardium Heart, February 1, 2001; 85(2): 208 - 212. [Abstract] [Full Text]
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M. S. Goligorsky, J. Chen, and S. Brodsky Workshop: Endothelial Cell Dysfunction Leading to Diabetic Nephropathy : Focus on Nitric Oxide Hypertension, February 1, 2001; 37(2): 744 - 748. [Abstract] [Full Text] [PDF]
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V. Schachinger, M.B. Britten, S. Dimmeler, and A.M. Zeiher NADH/NADPH oxidase p22 phox gene polymorphism is associated with improved coronary endothelial vasodilator function Eur. Heart J., January 1, 2001; 22(1): 96 - 101. [Abstract] [PDF]
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E. Verna, L. Ceriani, L. Giovanella, G. Binaghi, and S. Garancini "False-Positive" Myocardial Perfusion Scintigraphy Findings in Patients with Angiographically Normal Coronary Arteries: Insights from Intravascular Sonography Studies J. Nucl. Med., December 1, 2000; 41(12): 1935 - 1940. [Abstract] [Full Text] [PDF]
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T.-M. Lee, S.-F. Su, W.-Y. Suo, C.-Y. Lee, M.-F. Chen, Y.-T. Lee, and C.-H. Tsai Distension of urinary bladder induces exaggerated coronary constriction in smokers with early atherosclerosis Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2838 - H2845. [Abstract] [Full Text] [PDF]
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V. Schächinger, M. B. Britten, and A. M. Zeiher Prognostic Impact of Coronary Vasodilator Dysfunction on Adverse Long-Term Outcome of Coronary Heart Disease Circulation, October 3, 2000; (2000) 0. [Abstract] [Full Text]
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X. Zhang, H. Li, H. Jin, Z. Ebin, S. Brodsky, and M. S. Goligorsky Effects of homocysteine on endothelial nitric oxide production Am J Physiol Renal Physiol, October 1, 2000; 279(4): F671 - F678. [Abstract] [Full Text] [PDF]
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J. L. Houghton, T. A. Pearson, R. G. Reed, M. T. Torosoff, N. L. Henches, P. A. Kuhner, and E. F. Philbin Cholesterol Lowering With Pravastatin Improves Resistance Artery Endothelial Function : Report of Six Subjects With Normal Coronary Arteriograms Chest, September 1, 2000; 118(3): 756 - 760. [Abstract] [Full Text] [PDF]
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A Jeremias, C Spies, N A Herity, E Pomerantsev, P G Yock, P J Fitzgerald, and A C Yeung Coronary artery compliance and adaptive vessel remodelling in patients with stable and unstable coronary artery disease Heart, September 1, 2000; 84(3): 314 - 319. [Abstract] [Full Text] [PDF]
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S. Fichtlscherer, G. Rosenberger, D. H. Walter, S. Breuer, S. Dimmeler, and A. M. Zeiher Elevated C-Reactive Protein Levels and Impaired Endothelial Vasoreactivity in Patients With Coronary Artery Disease Circulation, August 29, 2000; 102(9): 1000 - 1006. [Abstract] [Full Text] [PDF]
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J. A. Vita, A. C. Yeung, M. Winniford, J. M. Hodgson, C. B. Treasure, J. L. Klein, S. Werns, M. Kern, D. Plotkin, W. J. Shih, et al. Effect of Cholesterol-Lowering Therapy on Coronary Endothelial Vasomotor Function in Patients With Coronary Artery Disease Circulation, August 22, 2000; 102(8): 846 - 851. [Abstract] [Full Text] [PDF]
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S. Taddei, F. Galetta, A. Virdis, L. Ghiadoni, G. Salvetti, F. Franzoni, C. Giusti, and A. Salvetti Physical Activity Prevents Age-Related Impairment in Nitric Oxide Availability in Elderly Athletes Circulation, June 27, 2000; 101(25): 2896 - 2901. [Abstract] [Full Text] [PDF]
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U. Landmesser, R. Merten, S. Spiekermann, K. Buttner, H. Drexler, and B. Hornig Vascular Extracellular Superoxide Dismutase Activity in Patients With Coronary Artery Disease : Relation to Endothelium-Dependent Vasodilation Circulation, May 16, 2000; 101(19): 2264 - 2270. [Abstract] [Full Text] [PDF]
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A. Blum, L. Hathaway, R. Mincemoyer, W. H. Schenke, M. Kirby, G. Csako, M. A. Waclawiw, J. A. Panza, and R. O. Cannon III Oral L-Arginine in Patients With Coronary Artery Disease on Medical Management Circulation, May 9, 2000; 101(18): 2160 - 2164. [Abstract] [Full Text] [PDF]
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E. Aptecar, E. Teiger, P. Dupouy, C. Benvenuti, M. J. Kern, J. Woscoboinik, S. Sediame, J. M. Pernes, A. Castaigne, D. Loisance, et al. Effects of bradykinin on coronary blood flow and vasomotion in transplant patients J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1607 - 1615. [Abstract] [Full Text] [PDF]
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K. L. McNeill, L. Fontana, D. L. Russell-Jones, I. Rajman, J. M. Ritter, and P. J. Chowienczyk Inhibitory effects of low-density lipoproteins from men with type II diabetes on endothelium-dependent relaxation J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1622 - 1627. [Abstract] [Full Text] [PDF]
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V. Schachinger, M. B. Britten, and A. M. Zeiher Prognostic Impact of Coronary Vasodilator Dysfunction on Adverse Long-Term Outcome of Coronary Heart Disease Circulation, April 25, 2000; 101(16): 1899 - 1906. [Abstract] [Full Text] [PDF]
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A. Cortella, S. Zambon, G. Sartore, F. Piarulli, A. Calabro, G. Crepaldi, and E. Manzato Calf and Forearm Blood Flow in Hypercholesterolemic Patients Angiology, April 1, 2000; 51(4): 309 - 318. [Abstract] [PDF]
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J. A. Suwaidi, S. Hamasaki, S. T. Higano, R. A. Nishimura, D. R. Holmes Jr, and A. Lerman Long-Term Follow-Up of Patients With Mild Coronary Artery Disease and Endothelial Dysfunction Circulation, March 7, 2000; 101(9): 948 - 954. [Abstract] [Full Text] [PDF]
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G. Heusch, D. Baumgart, P. Camici, W. Chilian, L. Gregorini, O. Hess, C. Indolfi, and O. Rimoldi {alpha}-Adrenergic Coronary Vasoconstriction and Myocardial Ischemia in Humans Circulation, February 15, 2000; 101(6): 689 - 694. [Abstract] [Full Text] [PDF]
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U. Limbruno, A. S. Petronio, G. Amoroso, R. Baglini, G. Paterni, A. Merelli, R. Mariotti, Raffaele De Caterina, and M. Mariani The Impact of Coronary Artery Disease on the Coronary Vasomotor Response to Nonionic Contrast Media Circulation, February 8, 2000; 101(5): 491 - 497. [Abstract] [Full Text] [PDF]
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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]
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T. Tokudome, K. Mizushige, K. Ohmori, K. Watanabe, Y. Takagi, Y. Takano, H. Matsuo, and K. Mizushige Neurogenic Regulation of Basal Tone of Coronary Artery with Mild Atherosclerosis in Humans: Observation Using Two-Dimensional Intravascular Ultrasound Angiology, December 1, 1999; 50(12): 989 - 996. [Abstract] [PDF]
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A P Mansur, C V Serrano Jr, J C Nicolau, L A M César, and J A F Ramires Effect of cholesterol lowering treatment on positive exercise tests in patients with hypercholesterolaemia and normal coronary angiograms Heart, December 1, 1999; 82(6): 689 - 693. [Abstract] [Full Text]
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Z.-q. Yan, A. Sirsjo, M.-L. Bochaton-Piallat, G. Gabbiani, and G. K. Hansson Augmented Expression of Inducible NO Synthase in Vascular Smooth Muscle Cells During Aging Is Associated With Enhanced NF-{kappa}B Activation Arterioscler Thromb Vasc Biol, December 1, 1999; 19(12): 2854 - 2862. [Abstract] [Full Text] [PDF]
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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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 H. Gobel, C. Ihling, J. Dentz, H. E. Schaefer, A. M. Zeiher, and G. Fraedrich Increased tissue endothelin-1-like immunoreactivity in the internal mammary artery of patients with diabetes or hypercholesterolemia modulates the graft flow in the peri-operative period Eur. J. Cardiothorac. Surg., October 1, 1999; 14(4): 367 - 372. [Abstract] [Full Text] [PDF]
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