Effect of L-arginine on human coronary endothelium-dependent and physiologic vasodilation

Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA. quyyumia@gwgate.nhlbi.nih.gov

OBJECTIVES: We hypothesized that L-arginine would improve abnormal coronary vasodilation in response to physiologic stress in patients with atherosclerosis and its risk factors by reversing coronary endothelial dysfunction. BACKGROUND: Studies have demonstrated that physiologic coronary vasodilation correlates with endothelial function and that L-arginine, the substrate for nitric oxide synthesis, improves the response to acetylcholine (Ach). METHODS: Changes in coronary blood flow and epicardial diameter response to Ach, adenosine and cardiac pacing were measured in 32 patients with coronary atherosclerosis or its risk factors and in 7 patients without risk factors and normal coronary angiograms. RESULTS: Intracoronary L-arginine did not alter baseline coronary vascular tone, but the epicardial and microvascular responses to Ach were enhanced (both p < 0.001). The improvement after L-arginine was greater in epicardial segments that initially constricted with Ach; similarly, L-arginine abolished microvascular constriction produced by higher doses of Ach. Thus, there was a negative correlation between the initial epicardial and vascular resistance responses to Ach and the magnitude of improvement with L-arginine (r = -0.55 and r = -0.50, respectively, p < 0.001). D-Arginine did not affect the responses to Ach, and adenosine responses were unchanged with L-arginine. Cardiac pacing-induced epicardial constriction was abolished by L-arginine, but microvascular dilation remained unaffected. CONCLUSIONS: Thus, L-arginine improved endothelium-dependent coronary epicardial and microvascular function in patients with endothelial dysfunction. Prevention of epicardial constriction during physiologic stress by L-arginine in patients with endothelial dysfunction may be of therapeutic value in the treatment of myocardial ischemia.

This article has been cited by other articles:

				M. Kakoki, H.-S. Kim, C.-J. S. Edgell, N. Maeda, O. Smithies, and D. L. Mattson Amino acids as modulators of endothelium-derived nitric oxide Am J Physiol Renal Physiol, August 1, 2006; 291(2): F297 - F304. [Abstract] [Full Text] [PDF]

				P. Voisine, J. Li, C. Bianchi, T. A. Khan, M. Ruel, S.-H. Xu, J. Feng, A. Rosinberg, T. Malik, Y. Nakai, et al. Effects of L-Arginine on Fibroblast Growth Factor 2-Induced Angiogenesis in a Model of Endothelial Dysfunction Circulation, August 30, 2005; 112(9_suppl): I-202 - I-207. [Abstract] [Full Text] [PDF]

				P. Voisine, C. Bianchi, T. A. Khan, M. Ruel, S.-H. Xu, J. Feng, J. Li, T. Malik, A. Rosinberg, and F. W. Sellke Normalization of coronary microvascular reactivity and improvement in myocardial perfusion by surgical vascular endothelial growth factor therapy combined with oral supplementation of L-arginine in a porcine model of endothelial dysfunction J. Thorac. Cardiovasc. Surg., June 1, 2005; 129(6): 1414 - 1420. [Abstract] [Full Text] [PDF]

				C. Zhang, T. W. Hein, W. Wang, M. W. Miller, T. W. Fossum, M. M. McDonald, J. D. Humphrey, and L. Kuo Upregulation of Vascular Arginase in Hypertension Decreases Nitric Oxide-Mediated Dilation of Coronary Arterioles Hypertension, December 1, 2004; 44(6): 935 - 943. [Abstract] [Full Text] [PDF]

				N. Gokce L-Arginine and Hypertension J. Nutr., October 1, 2004; 134(10): 2807S - 2811S. [Abstract] [Full Text] [PDF]

				S.E.S. Miner, A. Al-Hesayen, S. Kelly, T. Benson, J.J. Thiessen, V.R. Young, and J.D. Parker L-Arginine Transport in the Human Coronary and Peripheral Circulation Circulation, March 16, 2004; 109(10): 1278 - 1283. [Abstract] [Full Text] [PDF]

				J. Pernow, F. Bohm, E. Beltran, and A. Gonon L-Arginine protects from ischemia-reperfusion-induced endothelial dysfunction in humans in vivo J Appl Physiol, December 1, 2003; 95(6): 2218 - 2222. [Abstract] [Full Text]

				M. Ruel, G. F. Wu, T. A. Khan, P. Voisine, C. Bianchi, J. Li, J. Li, R. J. Laham, and F. W. Sellke Inhibition of the Cardiac Angiogenic Response to Surgical FGF-2 Therapy in a Swine Endothelial Dysfunction Model Circulation, September 9, 2003; 108(90101): II-335 - 340. [Abstract] [Full Text] [PDF]

				S. M Bode-Boger, J. Muke, A. Surdacki, G. Brabant, R. H Boger, and J. C Frolich Oral L-arginine improves endothelial function in healthy individuals older than 70 years Vascular Medicine, May 1, 2003; 8(2): 77 - 81. [Abstract] [PDF]

				K. Nakamura, S. Al-Ruzzeh, A. H. Chester, A. Dewar, S. Rothery, N. J. Severs, M. H. Yacoub, and M. Amrani Age-related changes in the protective effect of chronic administration of L-arginine on post-ischemic recovery of endothelial function Eur. J. Cardiothorac. Surg., April 1, 2003; 23(4): 626 - 632. [Abstract] [Full Text] [PDF]

				M. Weis and J. P. Cooke Cardiac Allograft Vasculopathy and Dysregulation of the NO Synthase Pathway Arterioscler. Thromb. Vasc. Biol., April 1, 2003; 23(4): 567 - 575. [Abstract] [Full Text] [PDF]

				J. L. Houghton, E. F. Philbin, D. S. Strogatz, M. T. Torosoff, S. A. Fein, P. A. Kuhner, V. E. Smith, and A. A. Carr The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine J. Am. Coll. Cardiol., April 17, 2002; 39(8): 1314 - 1322. [Abstract] [Full Text] [PDF]

				K. Nakamura, I. Schmidt, C. C. Gray, A. Dewar, S. Rothery, N. J. Severs, M. H. Yacoub, and M. Amrani The effect of chronic L-arginine administration on vascular recovery following cold cardioplegic arrest in rats Eur. J. Cardiothorac. Surg., April 1, 2002; 21(4): 753 - 759. [Abstract] [Full Text] [PDF]

				R. O. Cannon III Oral L-arginine (and other active ingredients) for ischemic heart disease? J. Am. Coll. Cardiol., January 2, 2002; 39(1): 46 - 48. [Full Text] [PDF]

				M. Imamura, S. Biro, T. Kihara, S. Yoshifuku, K. Takasaki, Y. Otsuji, S. Minagoe, Y. Toyama, and C. Tei Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1083 - 1088. [Abstract] [Full Text] [PDF]

				D Tousoulis, G J Davies, C Tentolouris, G Goumas, C Stefanadis, and P Toutouzas Vasomotor effects of L- and D-arginine in stenotic atheromatous coronary plaque Heart, September 1, 2001; 86(3): 296 - 301. [Abstract] [Full Text] [PDF]

				L. Schwartz and M. G. Bourassa Evaluation of Patients With Chest Pain and Normal Coronary Angiograms Arch Intern Med, August 13, 2001; 161(15): 1825 - 1833. [Full Text] [PDF]

				D. Behr-Roussel, A. Rupin, S. Simonet, E. Bonhomme, S. Coumailleau, A. Cordi, B. Serkiz, J.-N. Fabiani, and T. J. Verbeuren Effect of Chronic Treatment With the Inducible Nitric Oxide Synthase Inhibitor N-Iminoethyl-L-Lysine or With L-Arginine on Progression of Coronary and Aortic Atherosclerosis in Hypercholesterolemic Rabbits Circulation, August 29, 2000; 102(9): 1033 - 1038. [Abstract] [Full Text] [PDF]

				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]

				A. W. Wallace and W. L. Tom Interaction of L-Arginine and Phosphodiesterase Inhibitors in Vasodilation of the Porcine Internal Mammary Artery Anesth. Analg., April 1, 2000; 90(4): 840 - 846. [Abstract] [Full Text] [PDF]

				D Tousoulis, C Tentolouris, T Crake, G Katsimaglis, C Stefanadis, P Toutouzas, and G J Davies Effects of L- and D-arginine on the basal tone of human diseased coronary arteries and their responses to substance P Heart, May 1, 1999; 81(5): 505 - 511. [Abstract] [Full Text]

				A. Prasad, S. Husain, and A. A. Quyyumi Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin-converting enzyme inhibition: A potential role of bradykinin J. Am. Coll. Cardiol., March 1, 1999; 33(3): 796 - 804. [Abstract] [Full Text] [PDF]

				A. A. Quyyumi Does acute improvement of endothelial dysfunction in coronary artery disease improve myocardial ischemia?: A double-blind comparison of parenteral D- and L-Arginine J. Am. Coll. Cardiol., October 1, 1998; 32(4): 904 - 911. [Abstract] [Full Text] [PDF]

				R. O. Cannon III Role of nitric oxide in cardiovascular disease: focus on the endothelium Clin. Chem., August 1, 1998; 44(8): 1809 - 1819. [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]