Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium

Medical University, Department of Cardiology, Freiburg, Federal Republic of Germany.

The coronary vasomotor response to the cold pressor test was studied with use of quantitative coronary angiography in 32 patients without evidence of coronary artery disease and 55 patients with such disease; in a subset of 22 patients (9 with normal coronary arteries and 13 with coronary artery disease), the effects of the cold pressor test were compared with the effects of the endothelium-dependent vasodilator acetylcholine with simultaneous intracoronary Doppler flow velocity measurements to assess the influence of endothelial dysfunction. The cold pressor test induced vasodilation of 8.9 +/- 5.7% in all 77 analyzed vessel segments of the group with normal arteries (p less than 0.01). In contrast, in patients with coronary artery disease, the 52 analyzed stenotic segments were constricted by -12.1 +/- 9.5% (p less than 0.01), the 57 analyzed vessel segments with luminal irregularities were constricted by -8.9 +/- 5.2% (p less 0.01) and 40 (85%) of 47 angiographically normal segments also were constricted by -7.0 +/- 4.9% (p less than 0.05). Preserved vasodilating capability was demonstrated by intracoronary nitroglycerin in all analyzed segments. In nine patients with normal coronary arteries, the analyzed vessel segments were dilated in response to both the cold pressor test and intracoronary acetylcholine by 10.9 +/- 5.4% and 13.4 +/- 4.7%, respectively. In contrast, in all 13 patients with coronary artery disease, vasoconstriction of identical vessel segments by -9.1 +/- 3.7% and -23 +/- 10.4%, respectively, was observed after both the cold pressor test and intracoronary acetylcholine. Intracoronary propranolol did not significantly affect either the vasodilative response in 11 normal coronary arteries (11.3 +/- 4.4% before and 8.6 +/- 4.3% after beta-blockade) or the vasoconstrictor response in 8 atherosclerotic coronary arteries (-11.4 +/- 4.6% before and -14.6 +/- 5.3% after beta-blockade). The dilation of normal and the constriction of atherosclerotic coronary arteries with cold pressor testing exactly mirror the response to the endothelium-dependent dilator acetylcholine. Endothelial dysfunction in coronary atherosclerosis resulted in a loss of normal dilator function and permitted vasoconstrictor responses to sympathetic stimulation. Thus, coronary vasomotion of large epicardial arteries in response to sympathetic stimulation by the cold pressor test in humans is intimately related to the integrity of endothelial function.

This article has been cited by other articles:

				B. Biondi, M. Galderisi, L. Pagano, M. Sidiropulos, M. Pulcrano, A. D' Errico, S. Ippolito, A. Rossi, O. de Divitiis, and G. Lombardi Endothelial-mediated coronary flow reserve in patients with mild thyroid hormone deficiency Eur. J. Endocrinol., August 1, 2009; 161(2): 323 - 329. [Abstract] [Full Text] [PDF]

				A. Momen, V. Mascarenhas, A. Gahremanpour, Z. Gao, R. Moradkhan, A. Kunselman, J. P. Boehmer, L. I. Sinoway, and U. A. Leuenberger Coronary blood flow responses to physiological stress in humans Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H854 - H861. [Abstract] [Full Text] [PDF]

				H. Kawano, M. Tanimoto, K. Yamamoto, K. Sanada, Y. Gando, I. Tabata, M. Higuchi, and M. Miyachi Resistance training in men is associated with increased arterial stiffness and blood pressure but does not adversely affect endothelial function as measured by arterial reactivity to the cold pressor test Exp Physiol, February 1, 2008; 93(2): 296 - 302. [Abstract] [Full Text] [PDF]

				A. J. Flammer, F. Hermann, I. Sudano, L. Spieker, M. Hermann, K. A. Cooper, M. Serafini, T. F. Luscher, F. Ruschitzka, G. Noll, et al. Dark Chocolate Improves Coronary Vasomotion and Reduces Platelet Reactivity Circulation, November 20, 2007; 116(21): 2376 - 2382. [Abstract] [Full Text] [PDF]

				M. Naya, T. Tsukamoto, K. Morita, C. Katoh, T. Furumoto, S. Fujii, N. Tamaki, and H. Tsutsui Olmesartan, But Not Amlodipine, Improves Endothelium-Dependent Coronary Dilation in Hypertensive Patients J. Am. Coll. Cardiol., September 18, 2007; 50(12): 1144 - 1149. [Abstract] [Full Text] [PDF]

				P. T. Siegrist, O. Gaemperli, P. Koepfli, T. Schepis, M. Namdar, I. Valenta, F. Aiello, S. Fleischmann, H. Alkadhi, and P. A. Kaufmann Repeatability of Cold Pressor Test-Induced Flow Increase Assessed with H215O and PET J. Nucl. Med., September 1, 2006; 47(9): 1420 - 1426. [Abstract] [Full Text] [PDF]

				E. Nygard, K. F. Kofoed, J. Freiberg, S. Holm, J. Aldershvile, K. Eliasen, and H. Kelbaek Effects of High Thoracic Epidural Analgesia on Myocardial Blood Flow in Patients With Ischemic Heart Disease Circulation, May 3, 2005; 111(17): 2165 - 2170. [Abstract] [Full Text] [PDF]

				D. D. Gutterman, H. Miura, and Y. Liu Redox Modulation of Vascular Tone: Focus of Potassium Channel Mechanisms of Dilation Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 671 - 678. [Abstract] [Full Text] [PDF]

				A. Lerman and A. M. Zeiher Endothelial Function: Cardiac Events Circulation, January 25, 2005; 111(3): 363 - 368. [Full Text] [PDF]

				P. A. Kaufmann and P. G. Camici Myocardial Blood Flow Measurement by PET: Technical Aspects and Clinical Applications J. Nucl. Med., January 1, 2005; 46(1): 75 - 88. [Full Text] [PDF]

				T. H. Schindler, E. U. Nitzsche, M. Olschewski, N. Magosaki, M. Mix, J. O. Prior, A. D. Facta, U. Solzbach, H. Just, and H. R. Schelbert Chronic Inflammation and Impaired Coronary Vasoreactivity in Patients With Coronary Risk Factors Circulation, August 31, 2004; 110(9): 1069 - 1075. [Abstract] [Full Text] [PDF]

				M. Jorg-Ciopor, M. Namdar, J. Turina, R. Jenni, J. Schwitter, M. Turina, O. M. Hess, and P. A. Kaufmann Regional myocardial ischemia in hypertrophic cardiomyopathy: Impact of myectomy J. Thorac. Cardiovasc. Surg., August 1, 2004; 128(2): 163 - 169. [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]

				C. Duvernoy, J. Martin, K. Briesmiester, A. Bargardi, O. Muzik, and L. Mosca Myocardial Blood Flow and Flow Reserve in Response to Hormone Therapy in Postmenopausal Women with Risk Factors for Coronary Disease J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2783 - 2788. [Abstract] [Full Text] [PDF]

				T. H. Schindler, E. U. Nitzsche, M. Olschewski, I. Brink, M. Mix, J. Prior, A. Facta, M. Inubushi, H. Just, and H. R. Schelbert PET-Measured Responses of MBF to Cold Pressor Testing Correlate with Indices of Coronary Vasomotion on Quantitative Coronary Angiography J. Nucl. Med., March 1, 2004; 45(3): 419 - 428. [Abstract] [Full Text]

				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]

				T. H. Schindler, E. U. Nitzsche, T. Munzel, M. Olschewski, I. Brink, M. Jeserich, M. Mix, P. T. Buser, M. Pfisterer, U. Solzbach, et al. Coronary vasoregulation in patients with various risk factors in response to cold pressor testing: Contrasting myocardial blood flow responses to short- and long-term vitamin C administration J. Am. Coll. Cardiol., September 3, 2003; 42(5): 814 - 822. [Abstract] [Full Text] [PDF]

				T H Schindler, E Nitzsche, N Magosaki, I Brink, M Mix, M Olschewski, U Solzbach, and H Just Regional myocardial perfusion defects during exercise, as assessed by three dimensional integration of morphology and function, in relation to abnormal endothelium dependent vasoreactivity of the coronary microcirculation Heart, May 1, 2003; 89(5): 517 - 526. [Abstract] [Full Text] [PDF]

				G. Kudaiberdieva, B. Timuralp, N. Ata, A. Unalir, B. Gorenek, Y. Cavusoglu, O. Goktekin, and A. Birdane Cold Exposure and Left Ventricular Diastolic Performance In Coronary Artery Disease Angiology, March 1, 2003; 54(2): 187 - 193. [Abstract] [PDF]

				T. H. Schindler, B. Hornig, P. T. Buser, M. Olschewski, N. Magosaki, M. Pfisterer, E. U. Nitzsche, U. Solzbach, and H. Just Prognostic Value of Abnormal Vasoreactivity of Epicardial Coronary Arteries to Sympathetic Stimulation in Patients With Normal Coronary Angiograms Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 495 - 501. [Abstract] [Full Text] [PDF]

				A. Kjaer, C. Meyer, F. S. Nielsen, H.-H. Parving, and B. Hesse Dipyridamole, Cold Pressor Test, and Demonstration of Endothelial Dysfunction: A PET Study of Myocardial Perfusion in Diabetes J. Nucl. Med., January 1, 2003; 44(1): 19 - 23. [Abstract] [Full Text] [PDF]

				H. Furuyama, Y. Odagawa, C. Katoh, Y. Iwado, K. Yoshinaga, Y. Ito, K. Noriyasu, M. Mabuchi, Y. Kuge, K. Kobayashi, et al. Assessment of Coronary Function in Children With a History of Kawasaki Disease Using 15O-Water Positron Emission Tomography Circulation, June 18, 2002; 105(24): 2878 - 2884. [Abstract] [Full Text] [PDF]

				A. Nitenberg, S. Ledoux, P. Valensi, R. Sachs, and I. Antony Coronary Microvascular Adaptation to Myocardial Metabolic Demand Can Be Restored by Inhibition of Iron-Catalyzed Formation of Oxygen Free Radicals in Type 2 Diabetic Patients Diabetes, March 1, 2002; 51(3): 813 - 818. [Abstract] [Full Text] [PDF]

				T. Neunteufl, S. Heher, K. Kostner, G. Mitulovic, S. Lehr, G. Khoschsorur, R. W. Schmid, G. Maurer, and T. Stefenelli Contribution of nicotine to acute endothelial dysfunction in long-term smokers J. Am. Coll. Cardiol., January 16, 2002; 39(2): 251 - 256. [Abstract] [Full Text] [PDF]

				S. Simula, E. Vanninen, L. Viitanen, A. Kareinen, S. Lehto, P. Pajunen, M. Syvanne, J. Kuikka, M. Laakso, and J. Hartikainen Cardiac Adrenergic Innervation Is Affected in Asymptomatic Subjects with Very Early Stage of Coronary Artery Disease J. Nucl. Med., January 1, 2002; 43(1): 1 - 7. [Abstract] [Full Text] [PDF]

				A. Prasad, J. P. J. Halcox, M. A. Waclawiw, and A. A. Quyyumi Angiotensin type 1 receptor antagonism reverses abnormal coronary vasomotion in atherosclerosis J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1089 - 1095. [Abstract] [Full Text] [PDF]

				F. Tomai, F. Crea, A. Gaspardone, F. Versaci, A. S. Ghini, L. Chiariello, and P. A. Gioffre Unstable Angina and Elevated C-Reactive Protein Levels Predict Enhanced Vasoreactivity of the Culprit Lesion Circulation, September 25, 2001; 104(13): 1471 - 1476. [Abstract] [Full Text] [PDF]

				S. J. Duffy, E. S. Biegelsen, M. Holbrook, J. D. Russell, N. Gokce, J. F. Keaney Jr, and J. A. Vita Iron Chelation Improves Endothelial Function in Patients With Coronary Artery Disease Circulation, June 12, 2001; 103(23): 2799 - 2804. [Abstract] [Full Text] [PDF]

				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]

				M. Rubenfire, S. Rajagopalan, and L. Mosca Carotid artery vasoreactivity in response to sympathetic stress correlates with coronary disease risk and is independent of wall thickness J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2192 - 2197. [Abstract] [Full Text] [PDF]

				P. A. Kaufmann, T. Gnecchi-Ruscone, K. P. Schafers, T. F. Luscher, and P. G. Camici Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia J. Am. Coll. Cardiol., July 1, 2000; 36(1): 103 - 109. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				C. A. Schneider, E. Voth, D. Moka, F. M. Baer, J. Melin, A. Bol, R. Wagner, H. Schicha, E. Erdmann, and U. Sechtem Improvement of myocardial blood flow to ischemic regions by angiotensin- converting enzyme inhibition with quinaprilat IV: A study using [15O] water dobutamine stress positron emission tomography J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1005 - 1011. [Abstract] [Full Text] [PDF]

				D Tousoulis, C Tentolouris, T Crake, C Stefanadis, P Toutouzas, and G Davies Evidence of partially preserved endothelial dilator function in diseased coronary arteries Heart, October 1, 1999; 82(4): 471 - 476. [Abstract] [Full Text] [PDF]

				D. D. Gutterman Adventitia-dependent influences on vascular function Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1265 - H1272. [Full Text] [PDF]

				M. F. Di Carli, D. Bianco-Batlles, M. E. Landa, A. Kazmers, H. Groehn, O. Muzik, and G. Grunberger Effects of Autonomic Neuropathy on Coronary Blood Flow in Patients With Diabetes Mellitus Circulation, August 24, 1999; 100(8): 813 - 819. [Abstract] [Full Text] [PDF]

				H. Drexler Nitric oxide and coronary endothelial dysfunction in humans Cardiovasc Res, August 15, 1999; 43(3): 572 - 579. [Full Text] [PDF]

				J. Bartunek, W. Wijns, G. R. Heyndrickx, and B. de Bruyne Effects of Dobutamine on Coronary Stenosis Physiology and Morphology : Comparison With Intracoronary Adenosine Circulation, July 20, 1999; 100(3): 243 - 249. [Abstract] [Full Text] [PDF]

				T. F. Luscher and G. Noll Is It All in the Genes... ? : Nitric Oxide Synthase and Coronary Vasospasm Circulation, June 8, 1999; 99(22): 2855 - 2857. [Full Text] [PDF]

				D. Baumgart, M. Haude, G. Gorge, F. Liu, J. Ge, C. Große-Eggebrecht, R. Erbel, and G. Heusch Augmented {{alpha}}-Adrenergic Constriction of Atherosclerotic Human Coronary Arteries Circulation, April 27, 1999; 99(16): 2090 - 2097. [Abstract] [Full Text] [PDF]

				R. Campisi, J. Czernin, H. Schoder, J. W. Sayre, and H. R. Schelbert L-Arginine Normalizes Coronary Vasomotion in Long-Term Smokers Circulation, February 2, 1999; 99(4): 491 - 497. [Abstract] [Full Text] [PDF]

				R. Campisi, J. Czernin, H. Schoder, J. W. Sayre, F. D. Marengo, M. E. Phelps, and H. R. Schelbert Effects of Long-term Smoking on Myocardial Blood Flow, Coronary Vasomotion, and Vasodilator Capacity Circulation, July 14, 1998; 98(2): 119 - 125. [Abstract] [Full Text] [PDF]

				B. Ghaleh, L. Hittinger, S.-J. Kim, R. K. Kudej, M. Iwase, M. Uechi, A. Berdeaux, S. P. Bishop, and S. F. Vatner Selective large coronary endothelial dysfunction in conscious dogs with chronic coronary pressure overload Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H539 - H551. [Abstract] [Full Text] [PDF]

				B. G. Kral, L. C. Becker, R. S. Blumenthal, T. Aversano, L. A. Fleisher, R. M. Yook, and D. M. Becker Exaggerated Reactivity to Mental Stress Is Associated With Exercise-Induced Myocardial Ischemia in an Asymptomatic High-Risk Population Circulation, December 16, 1997; 96(12): 4246 - 4253. [Abstract] [Full Text]

				M. F. Di Carli, M. C. Tobes, T. Mangner, A. B. Levine, O. Muzik, P. Chakroborty, and T. B. Levine Effects of Cardiac Sympathetic Innervation on Coronary Blood Flow N. Engl. J. Med., April 24, 1997; 336(17): 1208 - 1216. [Abstract] [Full Text] [PDF]

				I. Antony, G. Lerebours, and A. Nitenberg Angiotensin-Converting Enzyme Inhibition Restores Flow-Dependent and Cold Pressor Test–Induced Dilations in Coronary Arteries of Hypertensive Patients Circulation, December 15, 1996; 94(12): 3115 - 3122. [Abstract] [Full Text]

				E. Aptecar, P. Dupouy, C. Benvenuti, J.-P. Mazzucotelli, E. Teiger, H. Geschwind, A. Castaigne, D. Loisance, and J.-L. Dubois-Rande Sympathetic Stimulation Overrides Flow-Mediated Endothelium-Dependent Epicardial Coronary Vasodilation in Transplant Patients Circulation, November 15, 1996; 94(10): 2542 - 2550. [Abstract] [Full Text]

				J. Cinca, A. Carreno, L. Mont, P. Blanch, and J. Soler-Soler Neurally Mediated Negative Inotropic Effect Impairs Myocardial Function During Cholinergic Coronary Vasoconstriction in Pigs Circulation, September 1, 1996; 94(5): 1101 - 1108. [Abstract] [Full Text]

				T. Kadokami, K. Egashira, K. Kuwata, Y. Fukumoto, T. Kozai, H. Yasutake, T. Kuga, H. Shimokawa, K. Sueishi, and A. Takeshita Altered Serotonin Receptor Subtypes Mediate Coronary Microvascular Hyperreactivityin Pigs With Chronic Inhibitionof Nitric Oxide Synthesis Circulation, July 15, 1996; 94(2): 182 - 189. [Abstract] [Full Text]

				H. El-Tamimi, M. Mansour, C. J. Pepine, T. J. Wargovich, and H. Chen Circadian Variation in Coronary Tone in Patients With Stable Angina : Protective Role of the Endothelium Circulation, December 1, 1995; 92(11): 3201 - 3205. [Abstract] [Full Text]

				V. Schachinger and A. M. Zeiher Quantitative Assessment of Coronary Vasoreactivity in Humans In Vivo : Importance of Baseline Vasomotor Tone in Atherosclerosis Circulation, October 15, 1995; 92(8): 2087 - 2094. [Abstract] [Full Text]

				A. M. Zeiher, V. Schachinger, and J. Minners Long-term Cigarette Smoking Impairs Endothelium-Dependent Coronary Arterial Vasodilator Function Circulation, September 1, 1995; 92(5): 1094 - 1100. [Abstract] [Full Text]

				T. Kuga, K. Egashira, M. Mohri, H. Tsutsui, Y. Harasawa, Y. Urabe, S. Ando, H. Shimokawa, and A. Takeshita Bradykinin-Induced Vasodilation Is Impaired at the Atherosclerotic Site but Is Preserved at the Spastic Site of Human Coronary Arteries In Vivo Circulation, July 15, 1995; 92(2): 183 - 189. [Abstract] [Full Text]

				A. M. Zeiher, T. Krause, V. Schachinger, J. Minners, and E. Moser Impaired Endothelium-Dependent Vasodilation of Coronary Resistance Vessels Is Associated With Exercise-Induced Myocardial Ischemia Circulation, May 1, 1995; 91(9): 2345 - 2352. [Abstract] [Full Text]

				I. Antony, G. Lerebours, and A. Nitenberg Loss of Flow-Dependent Coronary Artery Dilatation in Patients With Hypertension Circulation, March 15, 1995; 91(6): 1624 - 1628. [Abstract] [Full Text]