This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walker, H. A. Articles by Chowienczyk, P. J. Search for Related Content PubMed PubMed Citation Articles by Walker, H. A. Articles by Chowienczyk, P. J.

CLINICAL STUDY

Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina

Lack of effect of oral l-arginine on endothelial function, oxidative stress and exercise performance

Hamish A. Walker, MRCP^*, Elaine McGing^*, Ian Fisher, BSc, Rainer H. Böger, MD, Stefanie M. Bode-Böger, MD, Graham Jackson, FRCP^*, James M. Ritter, FRCP and Philip J. Chowienczyk, FRCP

^* Cardiothoracic Centre, St. Thomas’ Hospital, London, United Kingdom
Department of Clinical Pharmacology, Centre for Cardiovascular Medicine and Biology, King’s College, London, St. Thomas’ Hospital, London, United Kingdom
Department of Pharmacology, University Hospital, Hamburg-Eppendorf, Hamburg, Germany
Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

Manuscript received December 14, 2000; revised manuscript received March 29, 2001, accepted April 10, 2001.

Reprint requests and correspondence: Dr. P.J. Chowienczyk, Department of Clinical Pharmacology, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom
phil.chowienczyk{at}kcl.ac.uk

OBJECTIVES

This study was designed to determine the effect of two weeks’ treatment with L-arginine on the ratio of plasma L-arginine to asymmetric dimethylarginine (ADMA), oxidative stress, endothelium-dependent vasodilatation to acetylcholine, exercise performance and heart rate variability in men with stable angina.

BACKGROUND

The ratio of plasma L-arginine:ADMA has been proposed as a determinant of endothelium-dependent dilation; dietary supplementation with L-arginine has been shown to improve endothelium-dependent vasodilation and symptoms in some conditions.

METHODS

Men (n = 40) with stable angina, at least one epicardial coronary artery with a stenosis >50% and a positive exercise test were randomized to receive L-arginine (15 g daily) or placebo for two weeks according to a double-blind parallel-group design. Plasma L-arginine, ADMA, 8-epi-prostaglandin F₂ (a marker of oxidative stress) and forearm vasodilator responses to brachial artery infusion of nitroprusside and acetylcholine (±L-arginine) were measured. A standard Bruce protocol exercise test was performed before and at the end of the treatment period.

RESULTS

Plasma L-arginine increased after oral L-arginine, whereas ADMA remained unchanged, leading to an increase in the L-arginine/ADMA ratio of 62 ± 11% (mean ± SE, p < 0.01). Despite a significant enhancement in acetylcholine response by intra-arterial L-arginine at baseline, this response remained unchanged after oral L-arginine. Measures of oxidative stress and exercise performance after L-arginine/placebo were similar in placebo and active groups.

CONCLUSIONS

In men with stable angina, an increase in plasma L-arginine/ADMA ratio after two weeks’ oral supplementation with L-arginine is not associated with an improvement in endothelium-dependent vasodilatation, oxidative stress or exercise performance.

Abbreviations and Acronyms   ADMA = asymmetric dimethylarginine   AUC = area under forearm blood flow dose response curve   CAD = coronary artery disease   8-epi-PGF2 = 8-epi-prostaglandin-F2   LDL = low-density lipoprotein   NO = nitric oxide   NOS = nitric oxide synthase   SDMA = symmetric dimethylarginine

This article has been cited by other articles:

				T. K Rudolph, K. Ruempler, E. Schwedhelm, J. Tan-Andresen, U. Riederer, R. H Boger, and R. Maas Acute effects of various fast-food meals on vascular function and cardiovascular disease risk markers: the Hamburg Burger Trial Am. J. Clinical Nutrition, August 1, 2007; 86(2): 334 - 340. [Abstract] [Full Text] [PDF]

				R. H. Boger The Pharmacodynamics of L-Arginine J. Nutr., June 1, 2007; 137(6): 1650S - 1655S. [Abstract] [Full Text] [PDF]

				Z. Yang and X.-F. Ming Recent advances in understanding endothelial dysfunction in atherosclerosis. Clin. Med. Res., March 1, 2006; 4(1): 53 - 65. [Abstract] [Full Text] [PDF]

				G. K. McConell, N. N. Huynh, R. S. Lee-Young, B. J. Canny, and G. D. Wadley L-Arginine infusion increases glucose clearance during prolonged exercise in humans Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E60 - E66. [Abstract] [Full Text] [PDF]

				R. K Oka, A. Szuba, J. C Giacomini, and J. P Cooke A pilot study of l-arginine supplementation on functional capacity in peripheral arterial disease Vascular Medicine, November 1, 2005; 10(4): 265 - 274. [Abstract] [PDF]

				A. G. Herman and S. Moncada Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis Eur. Heart J., October 1, 2005; 26(19): 1945 - 1955. [Abstract] [Full Text] [PDF]

				T. K. Krempl, R. Maas, K. Sydow, T. Meinertz, R. H. Boger, and J. Kahler Elevation of asymmetric dimethylarginine in patients with unstable angina and recurrent cardiovascular events Eur. Heart J., September 2, 2005; 26(18): 1846 - 1851. [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]

				B. L. Goodwin, L. P. Solomonson, and D. C. Eichler Argininosuccinate Synthase Expression Is Required to Maintain Nitric Oxide Production and Cell Viability in Aortic Endothelial Cells J. Biol. Chem., April 30, 2004; 279(18): 18353 - 18360. [Abstract] [Full Text] [PDF]

				J. P. Cooke Asymmetrical Dimethylarginine: The Uber Marker? Circulation, April 20, 2004; 109(15): 1813 - 1818. [Full Text] [PDF]

				T. J. Bivalacqua, M. F. Usta, H. C. Champion, P. J. Kadowitz, and W. J. G. Hellstrom Endothelial Dysfunction in Erectile Dysfunction: Role of the Endothelium in Erectile Physiology and Disease J Androl, November 1, 2003; 24(6_suppl): S17 - S37. [Full Text] [PDF]

				R. H Boger The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor Cardiovasc Res, October 1, 2003; 59(4): 824 - 833. [Abstract] [Full Text] [PDF]

				J. P. Cooke, K. Sydow, J. Chen, and P. Huang A Peculiar Result and a Fanciful Hypothesis Regarding L-Arginine * Arterioscler. Thromb. Vasc. Biol., June 1, 2003; 23(6): 1128 - 1128. [Full Text] [PDF]

				N. Toda and T. Okamura The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels Pharmacol. Rev., June 1, 2003; 55(2): 271 - 324. [Abstract] [Full Text] [PDF]

				J. Loscalzo L-Arginine in Atherosclerosis: Consequences of Methylation Stress in a Complex Catabolism? Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 3 - 5. [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]