Review article: L-arginine as a nutritional prophylaxis against vascular endothelial dysfunction with aging

Journal of Cardiovascular Pharmacology and Therapeutics

Volumn 15, Issue 1, 2010, Pages 17-23

  Heffernan, Kevin S ^a,b   Fahs, Christopher A ^c   Ranadive, Sushant M ^c   Patvardhan, Eshan A ^a  

^a TUFTS MEDICAL CENTER   (United States)

^b TUFTS UNIVERSITY   (United States)

^c UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

Endothelial; Growth hormone; Inflammation; Vascular

Indexed keywords

ANTIINFLAMMATORY AGENT; ARGININE; GROWTH HORMONE; NITRIC OXIDE; PLACEBO;

AGING; CARDIOVASCULAR DISEASE; CARDIOVASCULAR FUNCTION; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DISEASE COURSE; HUMAN; NONHUMAN; NUTRITION; PLEIOTROPY; PRIORITY JOURNAL; PROPHYLAXIS; REVIEW; VASCULAR ENDOTHELIUM; VASCULITIS; DRUG EFFECT; ENDOTHELIUM CELL; METABOLISM; PATHOPHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME;

AGING; ANTI-INFLAMMATORY AGENTS; ARGININE; CARDIOVASCULAR DISEASES; ENDOTHELIAL CELLS; HUMANS; NITRIC OXIDE; NUTRITIONAL PHYSIOLOGICAL PHENOMENA; RANDOMIZED CONTROLLED TRIALS AS TOPIC; TREATMENT OUTCOME;

EID: 76649120507     PISSN: 10742484     EISSN: 19404034     Source Type: Journal    
DOI: 10.1177/1074248409354599     Document Type: Review

References (77)

1. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging heart in health: links to heart disease. Circulation. 2003 ; 107 (2). 346-354. (Pubitemid 36135235)
2. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a set up for vascular disease. Circulation. 2003 ; 107 (1). 139-146.
3. Csiszar A., Wang M., Lakatta EG, Ungvari Z. Inflammation and endothelial dysfunction during aging: role of NF-kappa B. J Appl Physiol. 2008 ; 105 (4). 1333-1341.
4. Heffernan KS, Vieira VJ, Valentine RJ Microvascular function and ageing L-arginine, tetrahydrobiopterin and the search for the fountain of vascular youth. J Physiol. 2008 ; 586 (8). 2041-2042.
5. Kuvin JT, Karas RH Clinical utility of endothelial function testing: ready for prime time ? Circulation. 2003 ; 107 (25). 3243-3247.
6. Deanfield JE, Halcox JP, Rabelink TJ Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007 ; 115 (10). 1285-1295.
7. Kuvin JT, Patel AR, Sliney KA, et al. Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease. J Am Coll Cardiol. 2001 ; 38 (7). 1843-1849.
8. Yavuz B. B, Yavuz B., Sener DD, et al. Advanced age is associated with endothelial dysfunction in healthy elderly subjects. Gerontology. 2008 ; 54 (3). 153-156.
9. Najjar SS, Scuteri A., Lakatta EG Arterial aging: Is it an immutable cardiovascular risk factor ? Hypertension. 2005 ; 46 (3). 454-462.
10. Kearney-Schwartz A., Rossignol P., Bracard S., et al. Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints. Stroke. 2009 ; 40 (4). 1229-1236.
11. Welsch MA, Dobrosielski DA, Arce-Esquivel AA, et al. The association between flow-mediated dilation and physical function in older men. Med Sci Sports Exerc. 2008 ; 40 (7). 1237-1243.
12. Brunner H., Cockcroft JR, Deanfield J., et al. Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005 ; 23 (2). 233-246. (Pubitemid 40279622)
13. Guazzi M., Reina G., Gripari P., Tumminello G., Vicenzi M., Arena R. Prognostic value of flow-mediated dilatation following myocardial infarction. Int J Cardiol. 2008 ; 132 (1). 45-50.
14. Deanfield J., Donald A., Ferri C., et al. Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005 ; 23 (1). 7-17. (Pubitemid 40128972)
15. Kitta Y., Obata JE, Nakamura T., et al. Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease. J Am Coll Cardiol. 2009 ; 53 (4). 323-330.
16. Suessenbacher A., Frick M., Alber HF, Barbieri V., Pachinger O., Weidinger F. Association of improvement of brachial artery flow-mediated vasodilation with cardiovascular events. Vasc Med. 2006 ; 11 (4). 239-244.
17. Modena MG, Bonetti L., Coppi F., Bursi F., Rossi R. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol. 2002 ; 40 (3). 505-510.
18. Michael SK, Surks HK, Wang Y., et al. High blood pressure arising from a defect in vascular function. Proc Natl Acad Sci U S A. 2008 ; 105 (8). 6702-6707.
19. Tang KM, Wang GR, Lu P., et al. Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat Med. 2003 ; 9 (12). 1506-1512.
20. Heffernan KS, Vieira VJ, Valentine RJ Microvascular function and ageing L-arginine, tetrahydrobiopterin and the search for the fountain of vascular youth. J Physiol. 2008 ; 586 (8). 2041-2042.
21. Delp MD, Behnke BJ, Spier SA, Wu G., Muller-Delp JM Ageing diminishes endothelium-dependent vasodilatation and tetrahydrobiopterin content in rat skeletal muscle arterioles. J Physiol. 2008 ; 586 (4). 1161-1168.
22. Wu G., Meininger CJ Arginine nutrition and cardiovascular function. J Nutr. 2000 ; 130 (11). 2626-2629.
23. Di Pasquale M. Amino Acids and Proteins for the Athlete. The Anabolic Edge. New York: CRC Press ; 1997.
24. Marchesi C., Paradis P., Schiffrin EL Role of the renin-angiotensin system in vascular inflammation. Trends Pharmacol Sci. 2008 ; 29 (7). 367-374.
25. Gornik HL, Creager MA Arginine and endothelial and vascular health. J Nutr. 2004 ; 134 (10 suppl). 2880S - 2887S ;discussion 2895S.
26. Preli RB, Klein KP, Herrington DM Vascular effects of dietary L-arginine supplementation. Atherosclerosis. 2002 ; 162 (1). 1-15.
27. Adams MR, McCredie R., Jessup W., Robinson J., Sullivan D., Celermajer DS. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease. Atherosclerosis. 1997 ; 129 (2). 261-269.
28. Clarkson P., Adams MR, Powe AJ, et al. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest. 1996 ; 97 (8). 1989-1994.
29. Bode-Boger SM, Muke J., Surdacki A., Brabant G., Boger RH, Frolich JC. Oral L-arginine improves endothelial function in healthy individuals older than 70 years. Vasc Med. 2003 ; 8 (2). 77-81.
30. Maxwell AJ, Zapien MP, Pearce GL, MacCallum G., Stone PH Randomized trial of a medical food for the dietary management of chronic, stable angina. J Am Coll Cardiol. 2002 ; 39 (1). 37-45.
31. Yin WH, Chen JW, Tsai C., Chiang MC, Young MS, Lin SJ L-arginine improves endothelial function and reduces LDL oxidation in patients with stable coronary artery disease. Clin Nutr. 2005 ; 24 (6). 988-997.
32. Sozykin AV, Noeva EA, Balakhonova TV, Pogorelova OA, Men'shikov M. Effect of L-arginine on platelet aggregation, endothelial function adn exercise tolerance in patients with stable angina pectoris [in Russian]. Ter Arkh. 2000 ; 72 (8). 24-27.
33. Jahangir E., Vita JA, Handy D., et al. The effect of l-arginine and creatine on vascular function and homocysteine metabolism. Vasc Med. 2009 ; 14 (3). 239-248.
34. Gates PE, Boucher ML, Silver AE, Monahan KD, Seals DR Impaired flow-mediated dilation with age is not explained by L-arginine bioavailability or endothelial asymmetric dimethylarginine protein expression. J Appl Physiol. 2007 ; 102 (1). 63-71.
35. Blum A., Hathaway L., Mincemoyer R., et al. Effects of oral L-arginine on endothelium-dependent vasodilation and markers of inflammation in healthy postmenopausal women. J Am Coll Cardiol. 2000 ; 35 (2). 271-276.
36. Chin-Dusting JP, Alexander CT, Arnold PJ, Hodgson WC, Lux AS, Jennings GL Effects of in vivo and in vitro L-arginine supplementation on healthy human vessels. J Cardiovasc Pharmacol. 1996 ; 28 (1). 158-166.
37. Adams MR, Forsyth CJ, Jessup W., Robinson J., Celermajer DS. Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. J Am Coll Cardiol. 1995 ; 26 (4). 1054-1061.
38. Bai Y., Sun L., Yang T., Sun K., Chen J., Hui R. 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 Clin Nutr. 2009 ; 89 (1). 77-84.
39. Boger RH, Bode-Boger SM, Thiele W., Creutzig A., Alexander K., Frolich JC Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol. 1998 ; 32 (5). 1336-1344.
40. Wilson AM, Harada R., Nair N., Balasubramanian N., Cooke JP L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation. 2007 ; 116 (2). 188-195.
41. Fahs CA, Heffernan KS, Fernhall B. Hemodynamic and vascular response to resistance exercise with L-arginine. Med Sci Sports Exerc. 2009 ; 41 (4). 773-779.
42. Mariotti F., Huneau JF, Szezepanski I., et al. Meal amino acids with varied levels of arginine do not affect postprandial vascular endothelial function in healthy young men. J Nutr. 2007 ; 137 (6). 1383-1389.
43. Lerman A., Burnett JC Jr, Higano ST, McKinley LJ, Holmes DR Jr. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation. 1998 ; 97 (21). 2123-2128.
44. Schulman SP, Becker LC, Kass DA, et al. L-arginine therapy in acute myocardial infarction: The Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA. 2006 ; 295 (1). 58-64.
45. Lin CC, Tsai WC, Chen JY, Li YH, Lin LJ, Chen JH Supplements of L-arginine attenuate the effects of high-fat meal on endothelial function and oxidative stress. Int J Cardiol. 2008 ; 127 (3). 337-341.
46. Marchesi S., Lupattelli G., Siepi D., et al. Oral L-arginine administration attenuates postprandial endothelial dysfunction in young healthy males. J Clin Pharm Ther. 2001 ; 26 (5). 343-349.
47. Siasos G., Tousoulis D., Vlachopoulos C., et al. The impact of oral l-arginine supplementation on acute smoking-induced endothelial injury and arterial performance. Am J Hypertens. 2009 ; 22 (6). 586-592.
48. Siasos G., Tousoulis D., Vlachopoulos C., et al. Short-term treatment with L-arginine prevents the smoking-induced impairment of endothelial function and vascular elastic properties in young individuals. Int J Cardiol. 2008 ; 126 (3). 394-399.
49. Beckman JS, Beckman TW, Chen J., Marshall PA, Freeman BA Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 ; 87 (4). 1620-1624.
50. Clapp BR, Hirschfield GM, Storry C., et al. Inflammation and endothelial function: direct vascular effects of human C-reactive protein on nitric oxide bioavailability. Circulation. 2005 ; 111 (12). 1530-1536.
51. Kals J., Kampus P., Kals M., et al. Inflammation and oxidative stress are associated differently with endothelial function and arterial stiffness in healthy subjects and in patients with atherosclerosis. Scand J Clin Lab Invest. 2008: 1-8 [Epub ahead of print].
52. Liuba P., Aburawi EH, Pesonen E., Andersson S., Yla-Herttuala S., Holmberg L. Residual adverse changes in arterial endothelial function and LDL oxidation after a mild systemic inflammation induced by influenza vaccination. Ann Med. 2007 ; 39 (5). 392-399.
53. Tousoulis D., Charakida M., Stefanadis C. Endothelial function and inflammation in coronary artery disease. Heart. 2006 ; 92 (4). 441-444.
54. Kharbanda RK, Walton B., Allen M., et al. Prevention of inflammation-induced endothelial dysfunction: a novel vasculo-protective action of aspirin. Circulation. 2002 ; 105 (22). 2600-2604.
55. Park KG, Hayes PD, Garlick PJ, Sewell H., Eremin O. Stimulation of lymphocyte natural cytotoxicity by L-arginine. Lancet. 1991 ; 337 (8742). 645-646.
56. Daly JM, Reynolds J., Sigal RK, Shou J., Liberman MD Effect of dietary protein and amino acids on immune function. Crit Care Med. 1990 ; 18 (2 suppl). S86 - S93.
57. Fujii S., Zhang L., Igarashi J., Kosaka H. L-arginine reverses p47phox and gp91phox expression induced by high salt in Dahl rats. Hypertension. 2003 ; 42 (5). 1014-1020.
58. El-Mesallamy HO, Abdel Hamid SG, Gad MZ Oxidative stress and asymmetric dimethylarginine are associated with cardiovascular complications in hemodialysis patients: improvements by L-arginine intake. Kidney Blood Press Res. 2008 ; 31 (3). 189-195.
59. West SG, Likos-Krick A., Brown P., Mariotti F. Oral L-arginine improves hemodynamic responses to stress and reduces plasma homocysteine in hypercholesterolemic men. J Nutr. 2005 ; 135 (2). 212-217.
60. McConell GK Effects of L-arginine supplementation on exercise metabolism. Curr Opin Clin Nutr Metab Care. 2007 ; 10 (1). 46-51.
61. Borucki K., Aronica S., Starke I., Luley C., Westphal S. Addition of 2.5g l-arginine in a fatty meal prevents the lipemia-induced endothelial dysfunction in healthy volunteers. Atherosclerosis. 2009 ; 205 (1). 251-254.
62. Kuboki K., Jiang ZY, Takahara N., et al. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin. Circulation. 2000 ; 101 (6). 676-681.
63. Zeng G., Quon MJ Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J Clin Invest. 1996 ; 98 (4). 894-898.
64. Khan AS, Sane DC, Wannenburg T., Sonntag WE Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system. Cardiovasc Res. 2002 ; 541: 25-35.
65. Collier SR, Casey DP, Kanaley JA Growth hormone responses to varying doses of oral arginine. Growth Horm IGF Res. 2005 ; 15 (2). 136-139.
66. Kanaley JA Growth hormone, arginine and exercise. Curr Opin Clin Nutr Metab Care. 2008 ; 11 (1). 50-54.
67. Pfeifer M., Verhovec R., Zizek B., Prezelj J., Poredos P., Clayton RN Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab. 1999 ; 84 (2). 453-457.
68. Pfeifer M., Verhovec R., Zizek B. Growth hormone (GH) and atherosclerosis: changes in morphology and function of major arteries during GH treatment. Growth Horm IGF Res. 1999 ; 9 (suppl A). 25-30.
69. Evans LM, Davies JS, Goodfellow J., Rees JA, Scanlon MF Endothelial dysfunction in hypopituitary adults with growth hormone deficiency. Clin Endocrinol (Oxf). 1999 ; 50 (4). 457-464.
70. Smith JC, Evans LM, Wilkinson I., et al. Effects of GH replacement on endothelial function and large-artery stiffness in GH-deficient adults: a randomized, double-blind, placebo-controlled study. Clin Endocrinol (Oxf). 2002 ; 56 (4). 493-501.
71. Evans LM, Davies JS, Anderson RA, et al. The effect of GH replacement therapy on endothelial function and oxidative stress in adult growth hormone deficiency. Eur J Endocrinol. 2000 ; 142 (3). 254-262.
72. Napoli R., Guardasole V., Angelini V., et al. Acute effects of growth hormone on vascular function in human subjects. J Clin Endocrinol Metab. 2003 ; 88 (6). 2817-2820.
73. Bode-Boger SM, Boger RH, Loffler M., Tsikas D., Brabant G., Frolich JC L-arginine stimulates NO-dependent vasodilation in healthy humans-effect of somatostatin pretreatment. J Investig Med. 1999 ; 47 (1). 43-50.
74. Csiszar A., Labinskyy N., Perez V., et al. Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice. Am J Physiol Heart Circ Physiol. 2008 ; 295 (5). H1882 - H1894.
75. Li G., Del Rincon JP, Jahn LA, et al. Growth hormone exerts acute vascular effects independent of systemic or muscle insulin-like growth factor I. J Clin Endocrinol Metab. 2008 ; 93 (4). 1379-1385.
76. Thum T., Fleissner F., Klink I., et al. Growth hormone treatment improves markers of systemic nitric oxide bioavailability via insulin-like growth factor-I. J Clin Endocrinol Metab. 2007 ; 92 (11). 4172-4179.
77. Brown-Borg HM, Rakoczy SG Growth hormone administration to long-living dwarf mice alters multiple components of the antioxidative defense system. Mech Ageing Dev. 2003 ; 124 (10-12). 1013-1024.