Published online before print January 13, 2003, doi: 10.1161/01.CIR.0000046489.24563.79
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;107:429.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Acute Intravenous L-Arginine Infusion Decreases Endothelin-1 Levels and Improves Endothelial Function in Patients With Angina Pectoris and Normal Coronary Arteriograms
Correlation With Asymmetric Dimethylarginine Levels
From Divisione di Medicina, Unità di Diabetologia, Endocrinologia e Malattie Metaboliche (P.P., L.D.M., E.S., P.L., E.G.), Cattedra di Clinica Medica Generale e Terapia Medica (G.P.), Università Vita-Salute (G.F., S.C., A.M.), Laboratorio di Tecniche Separative (I.F., R.P.), Dipartimento di Cardiologia e Scienze Cardiovascolari, Unità di Cardiologia Clinica, IRCCS H San Raffaele, Milano, Italy.
Correspondence to PierMarco Piatti, MD, IRCCS H San Raffaele, Via Olgettina 60, 20132 Milano, Italy. E-mail piermarco.piatti{at}hsr.it
Background— We tested the hypothesis that asymmetric dimethylarginine (ADMA) levels could be elevated and influence endothelin-1 and nitric oxide release and action in patients with cardiac syndrome X (CSX). In addition, we evaluated whether an intravenous infusion of L-arginine would improve endothelial function in these subjects.
Methods and Results— Nine patients with CSX and 14 control subjects underwent a continuous infusion of L-arginine (0.125 g/min) or saline for 120 minutes. Sixty minutes after L-arginine or saline infusions, an intravenous insulin bolus (0.1 U/kg) combined with a euglycemic clamp was performed. Basal ADMA and endothelin-1 levels were higher in patients with CSX than in controls. At the end of the first hour of infusion, compared with saline, L-arginine infusion increased basal forearm blood flow, nitrite and nitrate (NOx), and forearm cGMP release and decreased endothelin-1. After insulin bolus, during saline, insulin-induced NOx, endothelin-1, and forearm cGMP release was almost abolished. Conversely, L-arginine restored a physiological profile of all endothelial variables compared with control subjects. In control subjects, compared with saline infusion, L-arginine infusion did not modify any parameter. ADMA levels were positively correlated with basal endothelin-1 levels and negatively correlated with insulin-induced incremental levels of NOx and forearm cGMP release.
Conclusions— Plasma ADMA levels are increased in patients with CSX, and they are correlated with increases in endothelin-1 and reductions in insulin-induced increments in plasma NOx and cGMP, effects that are reversed by intravenous L-arginine. These data suggest that increased ADMA levels play a role in the abnormal vascular reactivity that is observed in patients with CSX.
Key Words: endothelin • nitric oxide • amino acids • angina • arteries
This article has been cited by other articles:
 |
|
 |
|
  Y. Bai, L. Sun, T. Yang, K. Sun, J. Chen, and R. Hui Increase in fasting vascular endothelial function after short-term oral L-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials Am. J. Clinical Nutrition, January 1, 2009; 89(1): 77 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Lteif, A. D. Fulford, R. V. Considine, I. Gelfand, A. D. Baron, and K. J. Mather Hyperinsulinemia fails to augment ET-1 action in the skeletal muscle vascular bed in vivo in humans Am J Physiol Endocrinol Metab, December 1, 2008; 295(6): E1510 - E1517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Nicholls, Z. Wang, R. Koeth, B. Levison, B. DelFraino, V. Dzavik, O. W. Griffith, D. Hathaway, J. A. Panza, S. E. Nissen, et al. Metabolic Profiling of Arginine and Nitric Oxide Pathways Predicts Hemodynamic Abnormalities and Mortality in Patients With Cardiogenic Shock After Acute Myocardial Infarction Circulation, November 13, 2007; 116(20): 2315 - 2324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Shmilovich, V. Deutsch, A. Roth, H. Miller, G. Keren, and J. George Circulating endothelial progenitor cells in patients with cardiac syndrome X Heart, September 1, 2007; 93(9): 1071 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Ignarro, M. L. Balestrieri, and C. Napoli Nutrition, physical activity, and cardiovascular disease: An update Cardiovasc Res, January 15, 2007; 73(2): 326 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lucotti, E. Setola, L. D. Monti, E. Galluccio, S. Costa, E. P. Sandoli, I. Fermo, G. Rabaiotti, R. Gatti, and P. Piatti Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E906 - E912. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Mittermayer, K. Krzyzanowska, M. Exner, W. Mlekusch, J. Amighi, S. Sabeti, E. Minar, M. Muller, M. Wolzt, and M. Schillinger Asymmetric Dimethylarginine Predicts Major Adverse Cardiovascular Events in Patients With Advanced Peripheral Artery Disease Arterioscler Thromb Vasc Biol, November 1, 2006; 26(11): 2536 - 2540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Napoli, S. Williams-Ignarro, F. de Nigris, L. O. Lerman, F. P. D'Armiento, E. Crimi, R. E. Byrns, A. Casamassimi, A. Lanza, F. Gombos, et al. Physical training and metabolic supplementation reduce spontaneous atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice PNAS, July 5, 2006; 103(27): 10479 - 10484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Shimabukuro, N. Higa, I. Chinen, K. Yamakawa, and N. Takasu Effects of a Single Administration of Acarbose on Postprandial Glucose Excursion and Endothelial Dysfunction in Type 2 Diabetic Patients: A Randomized Crossover Study J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 837 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Monti, E. Setola, G. Fragasso, R. P. Camisasca, P. Lucotti, E. Galluccio, A. Origgi, A. Margonato, and P. Piatti Metabolic and endothelial effects of trimetazidine on forearm skeletal muscle in patients with type 2 diabetes and ischemic cardiomyopathy Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E54 - E59. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Anthony, J. Leiper, and P. Vallance Endogenous production of nitric oxide synthase inhibitors Vascular Medicine, July 1, 2005; 10(1_suppl): S3 - S9. [Abstract] [PDF]
|
|
|
|
|
|
V.-P. Valkonen, T.-P. Tuomainen, and R. Laaksonen DDAH gene and cardiovascular risk Vascular Medicine, July 1, 2005; 10(1_suppl): S45 - S48. [Abstract] [PDF]
|
|
|
|
|
|
S. Anthony, J. Leiper, and P. Vallance Endogenous production of nitric oxide synthase inhibitors Vascular Medicine, May 1, 2005; 10(2_suppl): S3 - S9. [Abstract] [PDF]
|
|
|
|
|
|
V.-P. Valkonen, T.-P. Tuomainen, and R. Laaksonen DDAH gene and cardiovascular risk Vascular Medicine, May 1, 2005; 10(2_suppl): S45 - S48. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Koga, Y. Akita, J. Nishioka, S. Yatsuga, N. Povalko, Y. Tanabe, S. Fujimoto, and T. Matsuishi L-Arginine improves the symptoms of strokelike episodes in MELAS Neurology, February 22, 2005; 64(4): 710 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Gokce L-Arginine and Hypertension J. Nutr., October 1, 2004; 134(10): 2807S - 2811S. [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]
|
|
|
|
|
|
C. Napoli, S. Williams-Ignarro, F. de Nigris, L. O. Lerman, L. Rossi, C. Guarino, G. Mansueto, F. Di Tuoro, O. Pignalosa, G. De Rosa, et al. Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice PNAS, June 8, 2004; 101(23): 8797 - 8802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S Rosenson Statin therapy: new therapy for cardiac microvascular dysfunction Eur. Heart J., November 2, 2003; 24(22): 1993 - 1994. [Full Text] [PDF]
|
|
|
|
|
|
P. Piatti, C. Di Mario, L. D. Monti, G. Fragasso, F. Sgura, A. Caumo, E. Setola, P. Lucotti, E. Galluccio, C. Ronchi, et al. Association of Insulin Resistance, Hyperleptinemia, and Impaired Nitric Oxide Release With In-Stent Restenosis in Patients Undergoing Coronary Stenting Circulation, October 28, 2003; 108(17): 2074 - 2081. [Abstract] [Full Text] [PDF]
|
|