Arginine restores nitric oxide activity and inhibits monocyte accumulation after vascular injury in hypercholesterolemic rabbits

Section of Vascular Medicine, Stanford University, California 94305-5246, USA.

OBJECTIVES: This study sought to determine whether the alterations in vascular function and structure after balloon injury in hypercholesterolemic rabbits could be inhibited by dietary arginine. BACKGROUND: Administration of arginine (the nitric oxide [NO] precursor) restores vascular NO activity in hypercholesterolemic animals. We and other investigators have shown that enhancement of vascular NO activity can inhibit myointimal hyperplasia after vascular injury in normocholesterolemic animals. METHODS: Twenty-eight New Zealand White rabbits received either normal rabbit chow, 0.5% cholesterol diet or 0.5% cholesterol diet plus L-arginine hydrochloride (2.25% wt/vol) in the drinking water. After 6 weeks of dietary intervention, the left iliac artery of each animal was subjected to a balloon injury. Four weeks later, the iliac arteries were harvested for vascular reactivity studies and immunohistochemical analysis. RESULTS: Vascular injury induced intimal thickening that was largely composed of vascular smooth muscle cells and extracellular matrix. In the setting of hypercholesterolemia, vascular injury induced an exuberant myointimal lesion that was augmented by the accumulation of lipid-laden macrophages. Dietary arginine reduced intimal thickening in the injured vessels of hypercholes-terolemic animals and substantially inhibited the accumulation of macrophages in the lesion (from 28% to 5% of the lesion area, p < 0.001). CONCLUSIONS: We report that lesions induced by vascular injury in hypercholesterolemic animals are markedly reduced by oral administration of arginine. Moreover, we find that the nature of the lesion is altered, with a striking reduction in the percentage of macrophages comprising the lesion.

This article has been cited by other articles:

				A. M. Wilson, R. Harada, N. Nair, N. Balasubramanian, and J. P. Cooke L-Arginine Supplementation in Peripheral Arterial Disease: No Benefit and Possible Harm Circulation, July 10, 2007; 116(2): 188 - 195. [Abstract] [Full Text] [PDF]

				R. Schnabel, S. Blankenberg, E. Lubos, K. J. Lackner, H. J. Rupprecht, C. Espinola-Klein, N. Jachmann, F. Post, D. Peetz, C. Bickel, et al. Asymmetric Dimethylarginine and the Risk of Cardiovascular Events and Death in Patients With Coronary Artery Disease: Results from the AtheroGene Study Circ. Res., September 2, 2005; 97(5): e53 - e59. [Abstract] [Full Text] [PDF]

				H. L. Gornik and M. A. Creager Arginine and Endothelial and Vascular Health J. Nutr., October 1, 2004; 134(10): 2880S - 2887S. [Abstract] [Full Text] [PDF]

				M. C. Stuhlinger, R. K. Oka, E. E. Graf, I. Schmolzer, B. M. Upson, O. Kapoor, A. Szuba, M. R. Malinow, T. C. Wascher, O. Pachinger, et al. Endothelial Dysfunction Induced by Hyperhomocyst(e)inemia: Role of Asymmetric Dimethylarginine Circulation, August 26, 2003; 108(8): 933 - 938. [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]

				P. Vermeersch, Z. Nong, E. Stabile, O. Varenne, H. Gillijns, M. Pellens, N. Van Pelt, M. Hoylaerts, I. De Scheerder, D. Collen, et al. L-Arginine Administration Reduces Neointima Formation After Stent Injury in Rats by a Nitric Oxide-Mediated Mechanism Arterioscler Thromb Vasc Biol, October 1, 2001; 21(10): 1604 - 1609. [Abstract] [Full Text] [PDF]

				Y.-p. Sun, B.-q. Zhu, A. E. M. Browne, S. Pulukurthy, T. M. Chou, K. Sudhir, S. A. Glantz, P. C. Deedwania, K. Chatterjee, and W. W. Parmley Comparative Effects of ACE Inhibitors and an Angiotensin Receptor Blocker on Atherosclerosis and Vascular Function Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2001; 6(2): 175 - 181. [Abstract] [PDF]

				G. Lembo, N. De Luca, C. Battagli, G. Iovino, A. Aretini, M. Musicco, G. Frati, F. Pompeo, C. Vecchione., and B. Trimarco A Common Variant of Endothelial Nitric Oxide Synthase (Glu298Asp) Is an Independent Risk Factor for Carotid Atherosclerosis Stroke, March 1, 2001; 32(3): 735 - 740. [Abstract] [Full Text] [PDF]

				J. P. Cooke Does ADMA Cause Endothelial Dysfunction? Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2032 - 2037. [Abstract] [Full Text] [PDF]

				A. Fard, C. H. Tuck, J. A. Donis, R. Sciacca, M. R. Di Tullio, H. D. Wu, T. A. Bryant, N.-T. Chen, M. Torres-Tamayo, R. Ramasamy, et al. Acute Elevations of Plasma Asymmetric Dimethylarginine and Impaired Endothelial Function in Response to a High-Fat Meal in Patients With Type 2 Diabetes Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2039 - 2044. [Abstract] [Full Text] [PDF]

				Y.-P. Sun, N. C. Lu, W. W. Parmley, and C. B. Hollenbeck Effects of Cholesterol Diets on Vascular Function and Atherogenesis in Rabbits Exp Biol Med, July 1, 2000; 224(3): 166 - 171. [Abstract] [Full Text] [PDF]

				A. J Maxwell, B. E Anderson, and J. P Cooke Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar(R) Vascular Medicine, February 1, 2000; 5(1): 11 - 19. [Abstract] [PDF]

				J. Niebauer, S. P. Schwarzacher, M. Hayase, B. Wang, R. S. Kernoff, J. P. Cooke, and A. C. Yeung Local L-Arginine Delivery After Balloon Angioplasty Reduces Monocyte Binding and Induces Apoptosis Circulation, October 26, 1999; 100(17): 1830 - 1835. [Abstract] [Full Text] [PDF]

				H. Qian, V. Neplioueva, G. A. Shetty, K. M. Channon, and S. E. George Nitric Oxide Synthase Gene Therapy Rapidly Reduces Adhesion Molecule Expression and Inflammatory Cell Infiltration in Carotid Arteries of Cholesterol-Fed Rabbits Circulation, June 15, 1999; 99(23): 2979 - 2982. [Abstract] [Full Text] [PDF]

				H. Miyazaki, H. Matsuoka, J. P. Cooke, M. Usui, S. Ueda, S. Okuda, and T. Imaizumi Endogenous Nitric Oxide Synthase Inhibitor : A Novel Marker of Atherosclerosis Circulation, March 9, 1999; 99(9): 1141 - 1146. [Abstract] [Full Text] [PDF]

				O. Tangphao, S. Chalon, A. M Coulston, H. Moreno Jr, J. R Chan, J. P Cooke, B. B Hoffman, and T. F Blaschke L-arginine and nitric oxide-related compounds in plasma: comparison of normal and arginine-free diets in a 24-h crossover study Vascular Medicine, February 1, 1999; 4(1): 27 - 32. [Abstract] [PDF]

				X. L. Ma, B. L. Lopez, G.-L. Liu, T. A. Christopher, F. Gao, Y. Guo, G. Z. Feuerstein, R. R. Ruffolo Jr, F. C. Barone, and T.-L. Yue Hypercholesterolemia Impairs a Detoxification Mechanism Against Peroxynitrite and Renders the Vascular Tissue More Susceptible to Oxidative Injury Circ. Res., June 19, 1997; 80(6): 894 - 901. [Abstract] [Full Text]