From the Service de Physiologie et d'Explorations Fonctionnelles,
INSERM, Hôpital Louis Mourier, CHU Xavier-Bichat, Colombes, France
(A.N., F.P., S.L.), and Service d'Endocrinologie Diabetologue et
Nutrition, Hôpital Jean Verdier, Bondy, France (R.S., J-R.A., P.V.).
Correspondence to Alain Nitenberg, MD, Service de Physiologie et d'Explorations Fonctionnelles, INSERM U.426, Hôpital Louis Mourier, CHU Xavier-Bichat, 178, rue des Renouillers, F-92700 Colombes, France.
Abstract
Background—Acetylcholine produces
coronary artery (CA) constriction in diabetic patients,
suggesting an impairment of endothelium-dependent
dilation. In diabetes, multiple metabolic abnormalities may
inactivate nitric oxide through oxygen free radical
production.
Methods and Results—To examine the mechanism of this abnormal
response, two physiological tests (ie, a cold
pressor test [CPT] and coronary flow increase induced by an
injection of 10 mg papaverine [PAP] in the distal left anterior
descending CA) were performed before and after either
intravenous L-arginine (625 mg/minx10 minutes)
or intravenous deferoxamine (50 mg/minx10
minutes) in 22 normotensive nonsmoking diabetic patients with
angiographically normal CAs and normal cholesterol.
Coronary surface areas were measured with quantitative
angiography. Before the administration of L-arginine or
deferoxamine, CPT induced CA constriction in both groups
(-14±10% and -15±11%, respectively; each P<.001),
and PAP injection in distal LAD did not modify significantly proximal
LAD dimensions. In the 10 diabetic patients receiving
L-arginine, responses to CPT and PAP were not modified.
Conversely, in the 12 patients receiving deferoxamine, CA
dilated in response to the two tests (+10±9% after CPT and +22±7%
after PAP, each P<.001). Intracoronary
isosorbide dinitrate, an endothelium-independent
dilator, produced similar dilation in the two groups (+47±19% and
+41±15%, respectively; each P<.001).
Conclusions—This study shows that (1) responses of
angiographically normal CAs to CPT and to flow increase are impaired in
diabetic patients; (2) abnormal responses are not improved by
L-arginine, suggesting that a deficit in substrate for
nitric oxide synthesis is not involved; and (3)
deferoxamine restores a vasodilator response to the two
tests, suggesting that inactivation of NO by oxygen species might be
partly responsible for the impairment of CA dilation in diabetic
patients.
© 1998 American Heart Association, Inc.
Clinical Investigations and Reports
Coronary Artery Responses to Physiological Stimuli Are Improved by Deferoxamine but not by L-Arginine in Non–Insulin-Dependent Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Risk Factors
Key Words: antioxidants • coronary disease • diabetes mellitus • free radicals
This article has been cited by other articles:
 |
|
 |
|
  A. Lopez-Bermejo, J. Khosravi, W. Ricart, A. Castro, V. Hwa, K. L. Pratt, R. Casamitjana, R. G. Rosenfeld, and J. M. Fernandez-Real Insulin-Like Growth Factor Binding Protein-Related Protein 1 (IGFBP-rP1/MAC25) Is Linked to Endothelial-Dependent Vasodilation in High-Ferritin Type 2 Diabetes Diabetes Care, June 1, 2007; 30(6): 1615 - 1617. [Full Text] [PDF]
|
|
|
|
 |
|
 X. Gao, S. Belmadani, A. Picchi, X. Xu, B. J. Potter, N. Tewari-Singh, S. Capobianco, W. M. Chilian, and C. Zhang Tumor Necrosis Factor-{alpha} Induces Endothelial Dysfunction in Leprdb Mice Circulation, January 16, 2007; 115(2): 245 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M Yunker, J. S Parboosingh, H. E Conradson, P. Faris, P. J Bridge, J. Buithieu, L. M Title, F. Charbonneau, S. Verma, E. M Lonn, et al. The effect of iron status on vascular health Vascular Medicine, May 1, 2006; 11(2): 85 - 91. [Abstract] [PDF]
|
|
|
|
|
|
E. Cosson, I. Pham, P. Valensi, J. Paries, J.-R. Attali, and A. Nitenberg Impaired Coronary Endothelium-Dependent Vasodilation Is Associated With Microalbuminuria in Patients With Type 2 Diabetes and Angiographically Normal Coronary Arteries Diabetes Care, January 1, 2006; 29(1): 107 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ishizaka, K. Saito, I. Mori, G. Matsuzaki, M. Ohno, and R. Nagai Iron Chelation Suppresses Ferritin Upregulation and Attenuates Vascular Dysfunction in the Aorta of Angiotensin II-Infused Rats Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2282 - 2288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gellman, J. M. Hare, C. J. Lowenstein, G. Gerstenblith, V. Coombs, P. Langenberg, J. A. Brinker, and J. R. Resar L-Arginine Ameliorates the Abnormal Sympathetic Response of the Dysfunctional Human Coronary Microvasculature Angiology, January 1, 2004; 55(1): 1 - 8. [Abstract] [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. J. Anderson, J. Hubacek, D. G. Wyse, and M. L. Knudtson Effect of chelation therapy on endothelial function in patients with coronary artery disease: PATCH substudy J. Am. Coll. Cardiol., February 5, 2003; 41(3): 420 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Fernandez-Real, G. Penarroja, A. Castro, F. Garcia-Bragado, A. Lopez-Bermejo, and W. Ricart Blood Letting in High-Ferritin Type 2 Diabetes: Effects on vascular reactivity Diabetes Care, December 1, 2002; 25(12): 2249 - 2255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. T. Huynh and J. A. Tayek Oral Arginine Reduces Systemic Blood Pressure in Type 2 Diabetes: Its Potential Role in Nitric Oxide Generation J. Am. Coll. Nutr., October 1, 2002; 21(5): 422 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tousoulis, C. Antoniades, C. Tentolouris, G. Goumas, C. Stefanadis, and P. Toutouzas L-Arginine in cardiovascular disease: dream or reality? Vascular Medicine, August 1, 2002; 7(3): 203 - 211. [Abstract] [PDF]
|
|
|
|
|
|
H. Zheng, C. Dimayuga, A. Hudaihed, and S. D. Katz Effect of Dexrazoxane on Homocysteine-Induced Endothelial Dysfunction in Normal Subjects Arterioscler. Thromb. Vasc. Biol., July 1, 2002; 22(7): e15 - 18. [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]
|
|
|
|
 |
|
 M. Kelm Flow-mediated dilatation in human circulation: diagnostic and therapeutic aspects Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H1 - H5. [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]
|
|
|
|
|
|
A. Nitenberg, S. Ledoux, P. Valensi, R. Sachs, J.-R. Attali, and I. Antony Impairment of Coronary Microvascular Dilation in Response to Cold Pressor-Induced Sympathetic Stimulation in Type 2 Diabetic Patients With Abnormal Stress Thallium Imaging Diabetes, May 1, 2001; 50(5): 1180 - 1185. [Abstract] [Full Text]
|
|
|
|
|
|
R. Shurtz-Swirski, S. Sela, A. T. Herskovits, S. M. Shasha, G. Shapiro, L. Nasser, and B. Kristal Involvement of Peripheral Polymorphonuclear Leukocytes in Oxidative Stress and Inflammation in Type 2 Diabetic Patients Diabetes Care, January 1, 2001; 24(1): 104 - 110. [Abstract] [Full Text]
|
|
|
|
|
|
T. Hammoud, J.-F. Tanguay, and M. G. Bourassa Management of coronary artery disease: therapeutic options in patients with diabetes J. Am. Coll. Cardiol., August 1, 2000; 36(2): 355 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Butler, A. D. Morris, J. J. F. Belch, A. Hill, and A. D. Struthers Allopurinol Normalizes Endothelial Dysfunction in Type 2 Diabetics With Mild Hypertension Hypertension, March 1, 2000; 35(3): 746 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Schoder, D. H. Silverman, R. Campisi, J. W. Sayre, M. E. Phelps, H. R. Schelbert, and J. Czernin Regulation of myocardial blood flow response to mental stress in healthy individuals Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H360 - H366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Kersten and D. C. Warltier Modulation of the adaptive response to myocardial ischemia by coexisting disease Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H2268 - H2270. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rivard, M. Silver, D. Chen, M. Kearney, M. Magner, B. Annex, K. Peters, and J. M. Isner Rescue of Diabetes-Related Impairment of Angiogenesis by Intramuscular Gene Therapy with Adeno-VEGF Am. J. Pathol., February 1, 1999; 154(2): 355 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Soriano, P. Pacher, J. Mabley, L. Liaudet, and C. Szabo Rapid Reversal of the Diabetic Endothelial Dysfunction by Pharmacological Inhibition of Poly(ADP-Ribose) Polymerase Circ. Res., October 12, 2001; 89(8): 684 - 691. [Abstract] [Full Text] [PDF]
|
|