Skip to main content

L-Arginine

Its Role in Cardiovascular Therapy

  • Chapter
  • 149 Accesses

Part of the Contemporary Cardiology book series (CONCARD)

Abstract

A deficiency of nitric oxide (NO·) production and/or activity contributes to the pathophysiology and progression of a number of disorders or metabolic conditions associated with cardiovascular disease. Atherosclerosis and conditions predisposing to atherosclerosis (such as hypertension, hypercholesterolemia, tobacco use, estrogen deficiency, and age) are each associated with impaired endothelium-dependent vasodilation (1–10). Endothelium-dependent vasodilation is also attenuated in individuals suffering from such diverse diseases as renal insufficiency, heart failure, pulmonary hypertension, and in such conditions as ischemiareperfusion, transplant vasculopathy, and restenosis. The mechanisms underlying endothelial impairment are also varied. These include degradation of NO· (because of vascular generation of superoxide anion); inhibition of NO· synthesis (by endogenous antagonists of nitric oxide synthase [NOS]); alterations in NOS structure or function; reduced availability of the NO· precursor or NOS cofactors; and/or attenuated expression of NOS. Some of these disorders (hypercholesterolemia, tobacco use, and coronary and peripheral arterial disease) manifest an endothelial vasodilator dysfunction that is clearly responsive to administration of l-arginine, whereas in other disorders (such as long-standing hypertension or diabetes mellitus) the benefit of l-arginine is less clear.

Keywords

  • Nitric Oxide
  • Nitric Oxide
  • Pulmonary Hypertension
  • Peripheral Arterial Disease
  • Hypercholesterolemic Rabbit

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-59259-002-5_30
  • Chapter length: 39 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   269.00
Price excludes VAT (USA)
  • ISBN: 978-1-59259-002-5
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   349.99
Price excludes VAT (USA)
Hardcover Book
USD   349.99
Price excludes VAT (USA)

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Drexler H, Zeiher AM, Meinzer K, Just H. Correction of endothelial dysfunction in coronary micro-circulation of hypercholesterolaemic patients by L-arginine. Lancet 1991; 338: 1546–1550.

    PubMed  CAS  CrossRef  Google Scholar 

  2. Creager MA, Gallagher SJ, Girerd XJ, Coleman SM, Dzau VJ, et al. L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin Invest 1992; 90: 1248–1253.

    PubMed  CAS  CrossRef  Google Scholar 

  3. Clarkson P, Adams MR, Powe Ai, Donald AE, McCredie R, Robinson J, et al. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest 1996; 97: 1989–1994.

    PubMed  CAS  CrossRef  Google Scholar 

  4. Böger RH, Mugge A, Bode-Böger SM, Heinzel D, Hoper MM, Frolich JC. Differential systemic and pulmonary hemodynamic effects of L-arginine in patients with coronary artery disease or primary pulmonary hypertension. Int J Clin Pharmacol Ther 1996; 34: 323–328.

    PubMed  Google Scholar 

  5. Malczewska-Malec M, Goldsztajn P, Kawecka-Jaszcz K, Czarnecka D, Siedlecki A, Siemienska T, et al. Effects of prolonged L-arginine administration on blood pressure in patients with essential hypertension (EH). Agents Actions 1995; 45 (Suppl): 157–162.

    CAS  Google Scholar 

  6. Pagnatta P, Germano G, Grutter G, Leonardo F, Rosano GM, Chieria SL. Oral L-arginine supplementation improves essential hypertension. Circulation 1997; 96: I - 538.

    Google Scholar 

  7. Smulders RA, Stehouwer CD, Olthof CG, van Kamp GJ, Teerlink, T, de Vries PM, et al. Plasma endothelin levels and vascular effects of intravenous L-arginine infusion in subjects with uncomplicated insulin-dependent diabetes mellitus. Clin Sci (Colch) 1994; 87: 37–43.

    CAS  Google Scholar 

  8. Lubec B, Hayn M, Kitzmuller E, Vierhapper H, Lubec G. L-Arginine reduces lipid peroxidation in patients with diabetes mellitus. Free Rad Biol Med 1997; 22: 355–357.

    PubMed  CAS  CrossRef  Google Scholar 

  9. Adams MR, Jessup W, Celermajer DS. Cigarette smoking is associated with increased human monocyte adhesion to endothelial cells: reversibility with oral L-arginine but not vitamin C. J Am Coll Cardiol 1997; 29: 491–497.

    PubMed  CAS  CrossRef  Google Scholar 

  10. Chauhan A, More RS, Mullins PA, Taylor G, Petch C, Schofield PM. Aging-associated endothelial dysfunction in humans is reversed by L-arginine. J Am Coll Cardiol 1996; 28: 1796–1804.

    PubMed  CAS  CrossRef  Google Scholar 

  11. Higashi Y, Oshima T, Watanabe M, Matsuura H, Kajiyama G. Renal response to L-arginine in salt-sensitive patients with essential hypertension. Hypertension 1996; 27: 643–648.

    PubMed  CAS  CrossRef  Google Scholar 

  12. Higashi Y, Oshima T, Ozono R, Watanabe M, Matsuura H, Kajiyama G. Effects of L-arginine infusion on renal hemodynamics in patients with mild essential hypertension. Hypertension 1995; 25: 898–902.

    PubMed  CAS  CrossRef  Google Scholar 

  13. Campese VM, Amar M, Anjali C, Medhat T, Wurgaft A. Effect of L-arginine on systemic and renal haemodynamics in salt-sensitive patients with essential hypertension. J Hum Hypertens 1997; 11: 527–532.

    PubMed  CAS  CrossRef  Google Scholar 

  14. McCaffrey MJ, Bose CL, Reiter PD, Stiles AD. Effect of L-arginine infusion on infants with persistent pulmonary hypertension of the newborn. Biol Neonate 1995; 67: 240–243.

    PubMed  CAS  CrossRef  Google Scholar 

  15. Mehta S, Stewart DJ, Langleben D, Levy RD. Short-term pulmonary vasodilation with L-arginine in pulmonary hypertension. Circulation 1995; 92: 1539–1545.

    PubMed  CAS  CrossRef  Google Scholar 

  16. Surdacki A, Zmudka K, Bieron K, Kostka-Trabka E, Dubiel JS, Gryglewski RJ. Lack of beneficial effects of L-arginine infusion in primary pulmonary hypertension. Wien Klin Wochenschr 1994; 106: 521–526.

    PubMed  CAS  Google Scholar 

  17. Adams MR, Jessup W, McCredie R, 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. J Am Coll Cardiol 1997; 29: 387A.

    Google Scholar 

  18. Dubois-Rande JL, Zelinsky R, Chabrier PE, Castaigne A, Geschwind H, Adnot S. L-arginine improves endothelium-dependent relaxation of conductance and resistance coronary arteries in coronary artery disease. J Cardiovasc Pharmacol 1992; 20 (Suppl 12): S211–5213.

    PubMed  CrossRef  Google Scholar 

  19. Tagawa H, Mohri M, Ichiki T, Egashira K. L-arginine attemuates tachycardia-induced mayocardial ischemia in patients with extensive coronary artery disease. Circulation 1997; I (Suppl): 1–550.

    Google Scholar 

  20. 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: 261–269.

    PubMed  CAS  CrossRef  Google Scholar 

  21. Bode-Böger SM, Böger RH, Thiele W, Creutzig A, Frolich JC. L-arginine infusion therapy restores vascular NO production and improves the symptoms of intermittent claudication in patients with peripheral arterial disease. Circulation 1997; 96: 1–419.

    Google Scholar 

  22. Schellong SM, Böger RH, Burchert W, Bode-Böger SM, Galland A, Frölich JC, et al. Dose-related effect of intravenous L-arginine on muscular blood flow of the calf in patients with peripheral vascular disease: a H215O positron emission tomography study. Clin Sci (Colch) 1997; 93: 159–165.

    CAS  Google Scholar 

  23. Bode-Böger SM, Böger RH, Alfke H, Heinzel D, Tsikas D, Creutzig A, et al. L-arginine induces nitric oxide-dependent vasodilation in patients with critical limb ischemia. A randomized, controlled study. Circulation 1996; 93: 85–90.

    PubMed  CrossRef  Google Scholar 

  24. Wascher TC, Bahadori B, Habersack-Wallner S, Toplak H. Oral L-arginine supplementation in chronic heart failure. Circulation 1997; 95: 1674–1675.

    PubMed  CAS  Google Scholar 

  25. Kubota T, Imaizumi T, Oyama J, Ando S, Takeshita A. L-arginine increases exercise-induced vasodilation of the forearm in patients with heart failure. Jpn Circ J 1997; 61: 471–480.

    PubMed  CAS  CrossRef  Google Scholar 

  26. Hirooka Y, Imaizumi T, Tagawa T, Shiramoto M, Endo T, Ando S, et al. L-arginine on impaired acetylholine-induced and ischemic vasodilation of the forearm in patients with heart failure. Circulation 1994; 90: 658–668.

    PubMed  CAS  CrossRef  Google Scholar 

  27. Rector TS, Bank AJ, Mullen KA, Tschmumperlin LK, Sih R, Pillai K, et al. Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure. Circulation 1996; 93: 2135–2141.

    PubMed  CAS  CrossRef  Google Scholar 

  28. Chin-Dusting JP, Kaye DM, Lefkovits J, Wong J, Bergin P, Jennings GL. Dietary supplementation with L-arginine fails to restore endothelial function in forearm resistance arteries of patients with severe heart failure. J Am Coll Cardiol 1996; 27: 1207–1213.

    PubMed  CAS  CrossRef  Google Scholar 

  29. Drexler H, Fischell TA, Pinto FJ, Chenzbraun A, Botas J, Cooke JP, et al. Effect of L-arginine on coronary endothelial function in cardiac transplant recipients. Relation to vessel wall morphology. Circulation 1994; 89: 1615–1623.

    PubMed  CAS  CrossRef  Google Scholar 

  30. Paulus WJ, Kastner S, Vanderheyden M, Shah AM, Drexler H. Myocardial contractile effects of L-arginine in the human allograft. J Am Coll Cardiol 1997; 29: 1332–1338.

    PubMed  CAS  CrossRef  Google Scholar 

  31. Ebel M, Catapano G, Colombo MG, Clerico A, Giannessi D, del Chicca M, et al. The humoral, renal and pressor effects of systemic L-arginine infusion in hypertensive patients. J Hypertens 1993; 11 (Suppl 5): S140 - S141.

    CAS  CrossRef  Google Scholar 

  32. Wolf SC, Erley CM, Kenner S, Berger ED, Risler T. Does L-arginine alter proteinuria and renal hemodynamics in patients with chronic glomerulonephritis and hypertension? Clin Nephrol 1995; 43 (Suppl 1): S42 - S46.

    PubMed  Google Scholar 

  33. Hand MF, Haynes WG, Webb DJ. Hemodialysis and L-arginine, but not D-arginine, correct renal failure-associated endothelial dysfunction. Kidney Int 1998; 53: 1068–1077.

    PubMed  CAS  CrossRef  Google Scholar 

  34. Agostoni A, Marasini B, Biondi ML, Bassani C, Cazzaniga A, Bottasso B, et al. L-arginine therapy in Raynaud’ s phenomenon? International Journal of Clin Lab Res 1991; 21: 202–203.

    CAS  CrossRef  Google Scholar 

  35. Khan F, Litchfield SJ, McLaren M, Veale DJ, Littleford RC, Belch JJ. Oral L-arginine supplementation and cutaneous vascular responses in patients with primary Raynaud’s phenomenon. Arthritis Rheum 1997; 40: 352–357.

    PubMed  CAS  CrossRef  Google Scholar 

  36. Zorgniotti AW, Lizza EF. Effect of large doses of the nitric oxide precursor, L-arginine, on erectile dysfunction. Int J Impot Res 1994; 6: 33–35.

    PubMed  CAS  Google Scholar 

  37. Moody JA, Vernet D, Laidlaw S, Rajfer J, Gonzalez-Cadavid NF. Effects of long-term oral administration of L-arginine on the rat erectile response. J Urol 1997; 158: 942–947.

    PubMed  CAS  CrossRef  Google Scholar 

  38. Jovanovic A, Grbovic L, Tulic I. L-arginine induces relaxation of human uterine artery with both intact and denuded endothelium. Eur J Pharmacol 1994; 256: 103–107.

    PubMed  CAS  CrossRef  Google Scholar 

  39. Byrne BM, Howard RB, Morrow RJ, Whiteley KJ, Adamson SL. Role of the L-arginine nitric oxide pathway in hypoxic fetoplacental vasoconstriction. Placenta 1997; 18: 627–634.

    PubMed  CAS  CrossRef  Google Scholar 

  40. Neri I, Mazza V, Galassi MC, Volpe A, Facchinetti F. Effects of L-arginine on utero-placental circulation in growth-retarded fetuses. Acta Obstet Gynecol Scand 1996; 75: 208–212.

    PubMed  CAS  CrossRef  Google Scholar 

  41. Aji W, Ravalli S, Szabolcs M, Jiang XC, Sciacca RR, Michler RE, et al. L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice. Circulation 1997; 95: 430–437.

    PubMed  CAS  CrossRef  Google Scholar 

  42. Böger RH, Bode-Böger SM, Brandes RP, Phivthong-ngam L, Bohme M, Nafe R, et al. Dietary Larginine reduces the progression of atherosclerosis in cholesterol-fed rabbits: comparison with lovastatin. Circulation 1997; 96: 1282–1290.

    PubMed  CrossRef  Google Scholar 

  43. Candipan RC, Wang BY, Buitrago R, Tsao PS, Cooke JP. Regression or progression. Dependency on vascular nitric oxide. Arterioscl Thromb Vasc Biol 1996; 16: 44–50.

    PubMed  CAS  CrossRef  Google Scholar 

  44. Schwarzacher SP, Lim TT, Wang B, Kernoff RS, Niebauer J, Cooke JP, et al. Local intramural delivery of L-arginine enhances nitric oxide generation and inhibits lesion formation after balloon angioplasty. Circulation 1997; 95: 1863–1869.

    PubMed  CAS  CrossRef  Google Scholar 

  45. Greenlees C, Wadsworth RM, Martorana PA, Wainwright CL. The effects of L-arginine on neointimal formation and vascular function following balloon injury in heritable hyperlipidaemic rabbits. Cardiol Res 1997; 35: 351–359.

    CAS  Google Scholar 

  46. McNamara DB, Bedi B, Aurora H, Tena L, Ignarro LJ, Kadowitz PJ, et al. L-arginine inhibits balloon catheter-induced intimal hyperplasia. Biochem Biophys Res Commun 1993; 193: 291–296.

    PubMed  CAS  CrossRef  Google Scholar 

  47. Carrier M, Khalil A, Tourigny A, Solymoss BC, Pelletier LC. Effect of L-arginine on metabolic recovery of the ischemic myocardium. Ann Thorac Surg 1996; 61: 1651–1657.

    PubMed  CAS  CrossRef  Google Scholar 

  48. Engelman DT, Watanabe M, Maulik N, Cordis GA, Engelman RM, Rousou JA, et al. L-arginine reduces endothelial inflammation and myocardial stunning during ischemia/reperfusion. Ann Thorac Surgery 1995; 60: 1275–1281.

    CAS  CrossRef  Google Scholar 

  49. Shiraishi Y, Lee JR, Laks H, Waters PF, Meneshian A, Blitz A, et al. L-arginine administration during reperfusion improves pulmonary function. Ann Thorac Surgery 1996; 62: 1580–1587.

    CAS  CrossRef  Google Scholar 

  50. Wang QD, Morcos E, Wiklund P, Pernow J. L-arginine enhances functional recovery and Ca(2+)dependent nitric oxide synthase activity after ischemia and reperfusion in the rat heart. J Cardiovasc Pharmacol 1997; 29: 291–296.

    PubMed  CAS  CrossRef  Google Scholar 

  51. Sporer B, Martens KH, Koedel U, Haberl RL. L-arginine-induced regional cerebral blood flow increase is abolished after transient focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 1997; 17: 1074–1080.

    PubMed  CAS  CrossRef  Google Scholar 

  52. Nilsson B, Yoshida T, Delbro D, Andius S, Friman S. Pretreatment with L-arginine reduces ischemia/ reperfusion injury of the liver. Transplant Proc 1997; 29: 3111–3112.

    PubMed  CAS  CrossRef  Google Scholar 

  53. Ferraresso M, Burra P, Cadrobbi R, Calabrese F, Pettenazzo E, Sarzo G, et al. Protective effect of L-arginine on liver ischemia-reperfusion injury. Transplant Proc 1997; 29: 393–394.

    PubMed  CAS  CrossRef  Google Scholar 

  54. Amrani M, Gray CC, Smolenski RT, Goodwin AT, London A, Yacoub MH. The effect of L-arginine on myocardial recovery after cardioplegic arrest and ischemia under moderate and deep hypothermia. Circulation 1997;96: II-274-II-279.

    Google Scholar 

  55. Zhu B, Sun Y, Sievers RE, Glantz SA, Chatterjee K, Parmley WW. L-arginine decreases infarct size in rats exposed to environmental tobacco smoke. Am Heart J 1996; 132: 91–100.

    PubMed  CAS  CrossRef  Google Scholar 

  56. Barbul A, Rettura G, Levenson SM, Seifter E. Arginine: a thymotropic and wound-healing promoting agent. Surg Forum 1997; 28: 101–103.

    Google Scholar 

  57. Park KG, Hayes PD, Garlick Pi, Sewell H, Eremin O. Stimulation of lymphocyte natural cytotoxicity by L-arginine. Lancet 1991; 337: 645–646.

    PubMed  CAS  CrossRef  Google Scholar 

  58. Imler M, Ruscher H, Peter B, Kurtz D, Stahl J. [Action of arginine in a recurrent hepatic coma complicating a feminizing tumor of the adrenal cortex with hepatic metastases]. Sem Hop 1973; 49: 3183–3190.

    PubMed  CAS  Google Scholar 

  59. Batshaw ML, Wachtel RC, Thomas GH, Starrett A, Brusilow SW. Arginine-responsive asymptomatic hyperammonemia in the premature infant. J Pediatr 1984; 105: 86–91.

    PubMed  CAS  CrossRef  Google Scholar 

  60. Bellone J, Bartolotta E, Cardinale G, Arvat E, Cherubini V, Aimaretti G, et al. Low dose orally administered arginine is able to enhance both basal and growth hormone-releasing hormone-induced growth hormone secretion in normal short children. J Endo Invest 1993; 16: 521–525.

    CAS  Google Scholar 

  61. Brittenden J, Heys SD, Eremin O. L-arginine and malignant disease: a potential therapeutic role? Eur J Surg Oncol 1994; 20: 189–192.

    PubMed  CAS  Google Scholar 

  62. Rhodes P, Barr CS, Struthers AD. Arginine, lysine and ornithine as vasodilators in the forearm of man. Eur J Clin Invest 1996; 26: 325–331.

    PubMed  CAS  CrossRef  Google Scholar 

  63. Thomas G, Hecker M, Ramwell PW. Vascular activity of polycations and basic amino acids: L-arginine does not specifically elicit endothelium-dependent relaxation. Biochem Biophys Res Commun 1989; 158: 177–180.

    PubMed  CAS  CrossRef  Google Scholar 

  64. Wascher TC, Posch K, Wallner S, Hermetter A, Kostner GM, Graier WF. Vascular effects of L-arginine: anything beyond a substrate for the NO-synthase? Biochem Biophys Res Commun 1997; 234: 35–38.

    PubMed  CAS  CrossRef  Google Scholar 

  65. Korbonits M, Trainer PJ, Fanciulli G, Oliva O, Pala A, Dettori A, et al. L-arginine is unlikely to exert neuroendocrine effects in humans via the generation of nitric oxide. Eur J Endo 1996; 135: 543–547.

    CAS  CrossRef  Google Scholar 

  66. Blachier F, Mourtada A, Sener A, Malaisse WJ. Stimulus-secretion coupling of arginine-induced insulin release. Uptake of metabolized and nonmetabolized cationic amino acids by pancreatic islets. Endocrinology 1989; 124: 134–141.

    PubMed  CAS  CrossRef  Google Scholar 

  67. Reyes AA, Karl IE, Klahr S. Role of arginine in health and in renal disease. Am J Physiol 1994; 267: F331 - F346.

    PubMed  CAS  Google Scholar 

  68. Kirk SJ, Hurson M, Regan MC, Holt DR, Wasserkrug HL, Barbul A. Arginine stimulates wound healing and immune function in elderly human beings. Surgery 1993; 114: 155–160.

    PubMed  CAS  Google Scholar 

  69. Pegg AE, McCann PP. Polyamine metabolism and function. Am J Physiol 1982; 243: C212 - C221.

    PubMed  CAS  Google Scholar 

  70. Pollock JS, Forstermann U, Mitchell JA, Warner TD, Schmidt HH, Nakane M, et al. Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. Proc Natl Acad Sci USA 1991; 88: 10480–10484.

    PubMed  CAS  CrossRef  Google Scholar 

  71. Visek WJ. Arginine and disease states. J Nutr 1985; 115: 532–541.

    PubMed  CAS  Google Scholar 

  72. Hanssen H, Brunini TM, Conway M, Banning AP, Roberts NB, Ellory JC, et al. Increased L-arginine transport in human erythrocytes in chronic heart failure. Clin Sci (Colch) 1998; 94: 43–48.

    CAS  Google Scholar 

  73. FAO/WHO/UNU. Energy and Protein Requirements. Technical Report Series. WHO, Geneva, Switzerland, 1985.

    Google Scholar 

  74. Walser M. Urea cycle disorders and other hereditary hyperammonemic syndromes. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS, eds. The Metabolic Basis of Inherited Disease. McGraw-Hill, New York, 1983, pp. 402–438.

    Google Scholar 

  75. Visek WJ. Arginine needs, physiological state and usual diets. A reevaluation. J Nutr 1986; 116: 36–46.

    Google Scholar 

  76. Aisaka K, Gross SS, Griffith OW, Levi R. NG-methylarginine, an inhibitor of endothelium-derived nitric oxide synthesis, is a potent pressor agent in the guinea pig: does nitric oxide regulate blood pressure in vivo? Biochem Biophys Res Commun 1989; 160: 881–886.

    PubMed  CAS  CrossRef  Google Scholar 

  77. Aisaka K, Gross SS, Griffith OW, Levi R. L-arginine availability determines the duration of acetylcholine-induced systemic vasodilation in vivo. Biochem Biophys Res Commun 1989; 3: 710–717.

    CrossRef  Google Scholar 

  78. Rees DD, Palmer RM, Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 1989; 86: 3375–3378.

    PubMed  CAS  CrossRef  Google Scholar 

  79. Girerd XJ, Hirsch AT, Cooke JP, Dzau VJ, Creager MA. L-arginine augments endothelium-dependent vasodilation in cholesterol-fed rabbits. Circ Res 1990; 67: 1301–1308.

    PubMed  CAS  CrossRef  Google Scholar 

  80. Cooke JP, Andon NA, Girerd XJ, Hirsch AT, Creager MA. Arginine restores cholinergic relaxation of hypercholesterolemic rabbit thoracic aorta. Circulation 1991; 83: 1057–1062.

    PubMed  CAS  CrossRef  Google Scholar 

  81. Sato H, Zhao ZQ, Vinten-Johansen J. L-Arginine inhibits neutrophil adherence and coronary artery dysfunction. Cardiovasc Res 1996; 31: 63–72.

    PubMed  CAS  Google Scholar 

  82. Singer AH, Tsao PS, Wang BY, Bloch DA, Cooke JP. Discordant effects of dietary L-arginine on vascular structure and reactivity in hypercholesterolemic rabbits. J Cardiovasc Pharmacol 1995; 25: 710–716.

    PubMed  CAS  CrossRef  Google Scholar 

  83. Tsao PS, McEvoy LM, Drexler H, Butcher EC, Cooke JP. Enhanced endothelial adhesiveness in hypercholesterolemia is attenuated by L-arginine. Circulation 1994; 89: 2176–2182.

    PubMed  CAS  CrossRef  Google Scholar 

  84. Tsao PS, Theilmeier G, Singer AH, Leung LL, Cooke JP. L-arginine attenuates platelet reactivity in hypercholesterolemic rabbits. Arterioscl Thromb 1994; 14: 1529–1533.

    PubMed  CAS  CrossRef  Google Scholar 

  85. Liu J, Garcia-Cardena G, Sessa WC. Palmitoylation of endothelial nitric oxide synthase is necessary for optimal stimulated release of nitric oxide: implications for caveolae localization. Biochemistry 1996; 35: 13277–13281.

    PubMed  CAS  CrossRef  Google Scholar 

  86. Palmer RM, Moncada S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun 1989; 158: 348–352.

    PubMed  CAS  CrossRef  Google Scholar 

  87. Baydoun AR, Emery PW, Pearson JD, Mann GE. Substrate-dependent regulation of intracellular amino acid concentrations in cultured bovine aortic endothelial cells. Biochem Biophys Res Commun 1990; 73: 940–948.

    CrossRef  Google Scholar 

  88. Gold ME, Bush PA, Ignarro U. Depletion of arterial L-arginine causes reversible tolerance to endothelium-dependent relaxation. Biochem Biophys Res Commun 1989; 164: 714–721.

    PubMed  CAS  CrossRef  Google Scholar 

  89. Hecker M, Mitchell JA, Harris HJ, Katsura M, Thiemermann C, Vane JR. Endothelial cells metabolize NG-monomethyl-L-arginine to L-citrulline and subsequently to L-arginine. Biochem Biophys Res Commun 1990; 167: 1037–1043.

    PubMed  CAS  CrossRef  Google Scholar 

  90. Arnal JF, Munzel T, Venema RC, James NL, Bai CL, Mitch WE, et al. Interactions between L-arginine and L-glutamine change endothelial NO production. An effect independent of NO synthase substrate availability. J Clin Invest 1995; 95: 2565–2572.

    PubMed  CAS  CrossRef  Google Scholar 

  91. Förstermann U, Closs EI, Pollock JS, Nakane M, Schwartz P, Gath I, et al. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension 1994; 23: 1121–1131.

    PubMed  CrossRef  Google Scholar 

  92. Sessa WC, Hecker M, Mitchell JA, Vane JR. The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: L-glutamine inhibits the generation of L-arginine by cultured endothelial cells. Proc Natl Acad Sci USA 1990; 87: 8607–8611.

    PubMed  CAS  CrossRef  Google Scholar 

  93. Hecker M, Sessa WC, Harris HJ, Anggard EE, Vane JR. The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: cultured endothelial cells recycle L-citrulline to L-arginine. Proc Natl Acad Sci USA 1990; 87: 8612–8616.

    PubMed  CAS  CrossRef  Google Scholar 

  94. Swierkosz TA, Mitchell JA, Sessa WC, Hecker M, Vane JR. L-glutamine inhibits the release of endothelium-derived relaxing factor from the rabbit aorta. Biochem Biophys Res Commun 1990; 172: 143–148.

    PubMed  CAS  CrossRef  Google Scholar 

  95. Arnold WP, Mittal CK, Katsuki S, Murad F. Nitric oxide activates guanylate cyclase and increases guanosine 3’:5’-cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci USA 1977; 74: 3203–3207.

    PubMed  CAS  CrossRef  Google Scholar 

  96. McDonald KK, Zharikov S, Block ER, Kilberg MS. A caveolar complex between the cationic amino acid transporter 1 and endothelial nitric-oxide synthase may explain the “arginine paradox. ” J Biol Chem 1997; 272: 31213–31216.

    PubMed  CAS  CrossRef  Google Scholar 

  97. Garcia-Cardena G, Oh P, Liu J, Schnitzer JE, Sessa WC. Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling. Proc Natl Acad Sci USA 1996; 93: 6448–6453.

    PubMed  CAS  CrossRef  Google Scholar 

  98. Zharikov SI, Block ER. Characterization of L-arginine uptake by plasma membrane vesicles isolated from cultured pulmonary artery endothelial cells. Biochim Biophys Acta 1998; 1369: 173–183.

    PubMed  CAS  CrossRef  Google Scholar 

  99. Greene B, Pacitti Ai, Souba WW. Characterization of L-arginine transport by pulmonary artery endothelial cells. Am J Physiol 1993; 264: L351 - L356.

    PubMed  CAS  Google Scholar 

  100. Kavanaugh MP. Voltage dependence of facilitated arginine flux mediated by the system y+ basic amino acid transporter. Biochemistry 1993; 32: 5781–5785.

    PubMed  CAS  CrossRef  Google Scholar 

  101. Wang H, Kavanaugh MP, North RA, Kabat D. Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter [see comments]. Nature 1991; 352: 729–731.

    PubMed  CAS  CrossRef  Google Scholar 

  102. Zharikov SI, Herrera H, Block ER. Role of membrane potential in hypoxic inhibition of L-arginine uptake by lung endothelial cells. Am J Physiol 1997; 272: L78 - L84.

    PubMed  CAS  Google Scholar 

  103. Sobrevia L, Yudilevich DL, Mann GE. Activation of A2-purinoceptors by adenosine stimulates L-arginine transport (system y+) and nitric oxide synthesis in human fetal endothelial cells. J Physiol (Lond) 1997; 499: 135–140.

    CAS  Google Scholar 

  104. Sobrevia L, Mann GE. Dysfunction of the endothelial nitric oxide signalling pathway in diabetes and hyperglycaemia. Exp Physiol 1997; 82: 423–452.

    PubMed  CAS  Google Scholar 

  105. Cendan JC, Moldawer LL, Souba WW, Copeland EM, Lind DS. Endotoxin-induced nitric oxide production in pulmonary artery endothelial cells is regulated by cytokines. Arch Surg 1994; 129: 1296–1300.

    PubMed  CAS  CrossRef  Google Scholar 

  106. Cendan JC, Souba WW, Copeland EM, Lind DS. Cytokines regulate endotoxin stimulation of endothelial cell arginine transport. Surgery 1995; 117: 213–219.

    PubMed  CAS  CrossRef  Google Scholar 

  107. Lind DS, Copeland EM 3rd, Souba WW. Endotoxin stimulates arginine transport in pulmonary artery endothelial cells. Surgery 1993; 114: 199–205.

    PubMed  CAS  Google Scholar 

  108. Sobrevia L, Nadal A, Yudilevich DL, Mann GE. Activation of L-arginine transport (system y+) and nitric oxide synthase by elevated glucose and insulin in human endothelial cells. J Physiol (Lond) 1996; 490: 775–781.

    CAS  Google Scholar 

  109. Sobrevia L, Cesare P, Yudilevich DL, Mann GE. Diabetes-induced activation of system y+ and nitric oxide synthase in human endothelial cells: association with membrane hyperpolarization. J Physiol (Lond) 1995; 489: 183–192.

    CAS  Google Scholar 

  110. Chen LY, Mehta P, Mehta JL. Oxidized LDL decreases L-arginine uptake and nitric oxide synthase protein expression in human platelets: relevance of the effect of oxidized LDL on platelet function. Circulation 1996; 93: 1740–1746.

    PubMed  CAS  CrossRef  Google Scholar 

  111. Valiance P, Leone A, Calver A, Collier J, Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339: 572–575.

    CrossRef  Google Scholar 

  112. MacAllister RJ, Parry H, Kimoto M, Collier J, Moncada S. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. Br J Pharmacol 1996; 119: 1–8.

    CrossRef  Google Scholar 

  113. Bode-Böger SM, Boger RH, Kienke S, Junker W, Frolich JC. Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits. Biochem Biophys Res Commun 1996; 219: 598–603.

    PubMed  CrossRef  Google Scholar 

  114. Chan JR, Boger RH, Bode-Boger SM, Tangphao O, Tsao PS, Blaschke TF, et al. Restoration of L-arginine/ADMA ratio normalizes mononuclear leukocyte adhesiveness in hypercholesterolemic humans. Arterioscler Thromb Vasc Biol, in press.

    Google Scholar 

  115. Böger R, Bode Böger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, et al. Asymmetric Dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction. Its role in hypercholesterolemia. Circulation 1998; 98: 1842–1847.

    PubMed  CrossRef  Google Scholar 

  116. Faraci FM, Brian JE Jr, Heistad DD. Response of cerebral blood vessels to an endogenous inhibitor of nitric oxide synthase. Am J Physiol 1995; 269: H1522 - H1527.

    PubMed  CAS  Google Scholar 

  117. MacAllister RJ, Fickling SA, Whitley GS, Valiance P. Metabolism of methylarginines by human vasculature; implications for the regulation of nitric oxide synthesis. Br J Pharmacol 1994; 112: 43–48.

    PubMed  CAS  CrossRef  Google Scholar 

  118. Mendes Ribeiro AC, Hanssen H, Kiessling K, Roberts NB, Mann GE, Ellory JC. Transport of L-arginine and the nitric oxide inhibitor NG-monomethyl-L-arginine in human erythrocytes in chronic renal failure. Clin Sci (Colch) 1997; 93: 57–64.

    Google Scholar 

  119. Bogle RG, MacAllister RJ, Whitley GS, Valiance P. Induction of NG-monomethyl-L-arginine uptake: a mechanism for differential inhibition of NO synthases? Am J Physiol 1995; 269: C750 - C756.

    PubMed  CAS  Google Scholar 

  120. Pritchard KA Jr, Groszek L, Smalley DM, Sessa WC, Wu M, Villalon P, et al. Native low-density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion. Circ Res 1995; 77: 510–518.

    PubMed  CAS  CrossRef  Google Scholar 

  121. Huk I, Nanobashvili J, Neumayer C, Punz A, Mueller M, Afkhampour K, et al. L-arginine treatment alters the kinetics of nitric oxide and superoxide release and reduces ischemia/reperfusion injury in skeletal muscle. Circulation 1997; 96: 667–675.

    PubMed  CAS  CrossRef  Google Scholar 

  122. Stroes E, Kastelein J, Cosentino F, Erkelens W, Weyer R, Koomans H, et al. Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. J Clin Invest 1997; 99: 41–46.

    PubMed  CAS  CrossRef  Google Scholar 

  123. Schini VB, Vanhoutte PM. L-arginine evokes both endothelium-dependent and -independent relaxations in L-arginine-depleted aortas of the rat. Circ Res 1991; 68: 209–216.

    PubMed  CAS  CrossRef  Google Scholar 

  124. Fromm JR, Hileman RE, Caldwell EE, Weiler JM, Linhardt RJ. Differences in the interaction of heparin with arginine and lysine and the importance of these basic amino acids in the binding of heparin to acidic fibroblast growth factor. Arch Biochem Biophys 1995; 323: 279–287.

    PubMed  CAS  CrossRef  Google Scholar 

  125. Liu Z, Perlin AS. Regioselectivity in the sulfation of some chemically-modified heparins, and observations on their cation-binding characteristics. Carb Res 1992; 236: 121–133.

    CAS  CrossRef  Google Scholar 

  126. Fajans SS, Floyd JC Jr, Knopf RF, Conn FW. Effect of amino acids and proteins on insulin secretion in man. Recent Prog Horm Res 1967; 23: 617–662.

    PubMed  CAS  Google Scholar 

  127. Giugliano D, Marfella R, Verrazzo G, Acampora R, Coppola L, Cozzolino D, et al. The vascular effects of L-arginine in humans The role of endogenous insulin. J Clin Invest 1997; 99: 433–438.

    PubMed  CAS  CrossRef  Google Scholar 

  128. Sanchez A, Hubbard R. Dietary protein modulation of serum cholesterol: the amino acid connection. In: Freidman M, ed. Absorption and Utilization of Amino Acids. CRC Press, New York, 1990, pp. 247–273.

    Google Scholar 

  129. Ness GC, Zhao Z, Wiggins L. Insulin and glucagon modulate hepatic 3-hydroxy-3-methylglutarylcoenzyme A reductase activity by affecting immunoreactive protein levels. J Biol Chem 1994; 269: 29168–29172.

    PubMed  CAS  Google Scholar 

  130. Kritchevsky XX. Dietary protein and atherosclerosis. In: Freidman M, ed. Absorption and Utilization of Amino Acids. CRC Press, New York, 1990, pp. 235–245.

    Google Scholar 

  131. Sirtori CR, Galli G, Lovati MR, Carrara P, Bosisio E, Kienle MG. Effects of dietary proteins on the regulation of liver lipoprotein receptors in rats. J Nutr 1984; 114: 1493–1500.

    PubMed  CAS  Google Scholar 

  132. Barth CA, Pfeuffer M. Dietary protein and atherogenesis. Klin Wochenschr 1988; 66: 135–143.

    PubMed  CAS  CrossRef  Google Scholar 

  133. Kritchevsky D. Protein and atherosclerosis. J Nutr Sci Vitaminol (Tokyo) 1990; 36 (Suppl 2): S81 - S86.

    CrossRef  Google Scholar 

  134. Kurowska EM, Carroll KK. Hypocholesterolemic properties of nitric oxide. In vivo and in vitro studies using nitric oxide donors. Biochim Biophys Acta 1998; 1392: 41–50.

    PubMed  CAS  CrossRef  Google Scholar 

  135. Wascher TC, Graier WF, Dittrich P, Hussain MA, Bahadori B, Wallner S, et al. Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin sensitivity. EurJ Clin Invest 1997; 27: 690–695.

    CAS  CrossRef  Google Scholar 

  136. Miliutina NP, Ananian AA, Shugalei VS. [Antiradical and antioxidant effect of arginine and its action on lipid peroxidation in hypoxia]. Biull Eksp Biol Med 1990; 110: 263–265.

    PubMed  CAS  Google Scholar 

  137. Philis-Tsimikas A, Witztum JL. L-arginine may inhibit atherosclerosis through inhibition of LDL oxidation. Circulation 1995; 92: 1422–1443.

    CrossRef  Google Scholar 

  138. Xiong Y, Li YJ, Deng HW. Protection of 1-arginine against oxygen free radicals-injured rabbit aortic endothelium. Chung Kuo Yao Li Hsueh Pao 1994; 15: 119–123.

    PubMed  CAS  Google Scholar 

  139. Clancy RM, Leszczynska P, Piziak J, Abramson SB. Nitric oxide, an endothelial cell relation factor, inhibits neutrophil superoxide anion production via a direct action of NADPH oxidase. J Clin Invest 1992; 90: 1116–1121.

    PubMed  CAS  CrossRef  Google Scholar 

  140. Peng HB, Libby P, Liao JK. Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B. J Biol Chem 1995; 270: 14214–14219.

    PubMed  CAS  CrossRef  Google Scholar 

  141. Tsao PS, Wang B, Buitrago R, Shyy JY, Cooke JP. Nitric oxide regulates monocyte chemotactic protein-1. Circulation 1997; 96: 934–940.

    PubMed  CAS  CrossRef  Google Scholar 

  142. Higashi Y, Oshima T, Ono N, Hiraga H, Yoshimura M, Watanabe M, et al. Intravenous administration of L-arginine inhibits angiotensin-converting enzyme in humans. J Clin Endocrinol Metab 1995; 80: 2198–2202.

    PubMed  CAS  CrossRef  Google Scholar 

  143. Barbul A, Fishel RS, Shimazu S, Wasserkrug HL, Yoshimura NN, Tao RC, et al. Intravenous hyper-alimentation with high arginine levels improves wound healing and immune function. J Surg Res 1985; 38: 328–334.

    PubMed  CAS  CrossRef  Google Scholar 

  144. Nirgiotis JG, Hennessey PJ, Andrassy RJ. Effects of an arginine-free enteral diet on wound healing and immune function in the postsurgical rat. J Ped Surg 1991; 26: 936–941.

    CAS  CrossRef  Google Scholar 

  145. Seifter E, Rettura G, Barbul A, Levenson SM. Arginine: an essential amino acid for injured rats. Surgery 1978; 84: 224–230.

    PubMed  CAS  Google Scholar 

  146. Barbul A, Rettura G, Levenson SM, Seifter E. Wound healing and thymotropic effects of arginine: a pituitary mechanism of action. Am J Clin Nutr 1983; 37: 786–794.

    PubMed  CAS  Google Scholar 

  147. Heys SD, Gough DB, Park KGM, Eremin O. L-arginine: clinical practice and potential applications. In: Eremin O, ed. L-Arginine: Biological Aspects and Clinical Applications. Chapman & Hall, Austin, TX, 1997, pp. 115–157.

    Google Scholar 

  148. Micieli G, Bosone D, Costa A, Cavallini A, Marchesselli S, Pompeo F, et al. Opposite effects of L-arginine and nitroglycerin on cerebral blood velocity: nitric oxide precursors and cerebral blood velocity. J Neurol Sci 1997; 150: 71–75.

    PubMed  CAS  CrossRef  Google Scholar 

  149. Reutens DC, McHugh MD, Toussaint PJ, Evans AC, Gjedde A, Meyer E, et al. L-arginine infusion increases basal but not activated cerebral blood flow in humans. J Cereb Blood Flow Metab 1997; 17: 309–315.

    PubMed  CAS  CrossRef  Google Scholar 

  150. Cooke JP, Dzau J, Creager A. Endothelial dysfunction in hypercholesterolemia is corrected by L-arginine. Basic Res Cardiol 1991; 86 (Suppl 2): 173–181.

    PubMed  Google Scholar 

  151. Cooke JP, Singer AH, Tsao P, Zera P, Rowan RA, Billingham ME. Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit. J Clin Invest 1992; 90: 1168–7112.

    PubMed  CAS  CrossRef  Google Scholar 

  152. Davies MG, Dalen H, Kim JH, Barber L, Svendsen E, Hagen PO. Control of accelerated vein graft atheroma with the nitric oxide precursor: L-arginine. J Surg Res 1995; 59: 35–42.

    PubMed  CAS  CrossRef  Google Scholar 

  153. Jeremy RW, McCarron H, Sullivan D. Effects of dietary L-arginine on atherosclerosis and endothelium-dependent vasodilatation in the hypercholesterolemic rabbit. Response according to treatment duration, anatomic site, and sex. Circulation 1996; 94: 498–506.

    PubMed  CAS  CrossRef  Google Scholar 

  154. Randall MD, Ujiie H, Griffith TM. L-arginine reverses the impairment of nitric oxide-dependent collateral perfusion in dietary-induced hypercholesterolaemia in the rabbit. Clini Sci (Colch) 1994; 87: 53–59.

    CAS  Google Scholar 

  155. Rossitch E Jr, Alexander ED, Black PM, Cooke JP. L-arginine normalizes endothelial function in cerebral vessels from hypercholesterolemic rabbits. J Clin Invest 1991; 87: 1295–1299.

    PubMed  CAS  CrossRef  Google Scholar 

  156. Schuschke DA, Miller FN, Lominadze DG, Feldhoff RC. L-arginine restores cholesterol-attenuated microvascular responses in the rat cremaster. Int J Microcirc Clin Exp 1994; 14: 204–211.

    PubMed  CAS  CrossRef  Google Scholar 

  157. Kuo L, Davis MJ, Cannon MS, Chilian WM. Pathophysiological consequences of atherosclerosis extend into the coronary microcirculation. Restoration of endothelium-dependent responses by L-arginine. Circ Res 1992; 70: 465–476.

    PubMed  CAS  CrossRef  Google Scholar 

  158. Clarkson PB, Lim PO, MacDonald TM. Influence of basal nitric oxide secretion on cardiac function in man. Br J Clin Pharmacol 1995; 40: 299–305.

    PubMed  CAS  CrossRef  Google Scholar 

  159. Chowienczyk PJ, Watts GF, Cockcroft JR, Brett SE, Ritter JM. Sex differences in endothelial function in normal and hypercholesterolaemic subjects. Lancet 1994; 344: 305, 306.

    Google Scholar 

  160. Stroes ES, Koomans HA, de Bruin TW, Rabelink TJ. Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication. Lancet 1995; 346: 467–471.

    PubMed  CAS  CrossRef  Google Scholar 

  161. Goode GK, Heagerty AM. In vitro responses of human peripheral small arteries in hypercholesterolemia and effects of therapy. Circulation 1995; 91: 2898–2903.

    PubMed  CAS  CrossRef  Google Scholar 

  162. Wennmalm A. Endothelial nitric oxide and cardiovascular disease. J Int Med 1994; 35: 317–327.

    CrossRef  Google Scholar 

  163. Casino PR, Kilcoyne CM, Quyyumi AA, Hoeg JM, Panza JA. Investigation of decreased availability of nitric oxide precursor as the mechanism responsible for impaired endothelium-dependent vasodilation in hypercholesterolemic patients. J Am Coll Cardiol 1994; 23: 844–850.

    PubMed  CAS  CrossRef  Google Scholar 

  164. Maxwell AJ, Anderson B, Cooke JP. Endothelial dysfunction in hypercholesterolemia is reversed by a nutritional product designed to enhance nitric oxide activity. Cardiovasc Drugs Ther, in press.

    Google Scholar 

  165. Taddei S, Virdis A, Mattei P, Ghiadoni L, Sudano I, Salvetti A. Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation 1996; 94: 1298–1303.

    PubMed  CAS  CrossRef  Google Scholar 

  166. Kitazono T, Faraci FM, Heistad DD. L-arginine restores dilator responses of the basilar artery to acetylcholine during chronic hypertension. Hypertension 1996; 27: 893–896.

    PubMed  CAS  CrossRef  Google Scholar 

  167. Hayakawa H, Hirata Y, Suzuki E, Kimura K, Kikuchi K, Nagano T, et al. Long-term administration of L-arginine improves nitric oxide release from kidney in deoxycorticosterone acetate-salt hypertensive rats. Hypertension 1994; 23: 752–756.

    PubMed  CAS  CrossRef  Google Scholar 

  168. Hind JM, Doodson AC. Oral L-arginine supplementation has no effect on cardiovascular responses to lower body negative pressure in man. Clin Auton Res 1994; 4: 293–297.

    PubMed  CAS  CrossRef  Google Scholar 

  169. Rosano GM, Panina G, Cerquetani E, Leonardo F, Pelliccia F, Bonfigli B, et al. L-arginine improves endothelial function in newly diagnosed hypertensives. J Am Coll Cardiol 1998; 31: 262A (abstract).

    Google Scholar 

  170. Adnot S, Raffestin B, Eddahibi S, Braquet P, Chabrier PE. Loss of endothelium-dependent relaxant activity in the pulmonary circulation of rats exposed to chronic hypoxia. J Clin Invest 1991; 87: 155–162.

    PubMed  CAS  CrossRef  Google Scholar 

  171. Fineman JR, Chang R, Soifer SJ. L-Arginine, a precursor of EDRF in vitro, produces pulmonary vasodilation in lambs. Am J Physiol 1991; 261: H1563 - H1569.

    PubMed  CAS  Google Scholar 

  172. Eddahibi S, Adnot S, Carville C, Blouquit Y, Raffestin B. L-arginine restores endothelium-dependent relaxation in pulmonary circulation of chronically hypoxic rats. Am J Physiol 1992; 263: L194 - L200.

    PubMed  CAS  Google Scholar 

  173. Hui S, Mei Q, Qiu B. Effects of chronic nicotine ingestion on pressor response to N omega-nitro-L-arginine methyl ester and ex vivo concentration and relaxation response of aorta to L-arginine. Pharmacol Res 1997; 36: 451–456.

    CAS  Google Scholar 

  174. Hutchison SJ, Reitz MS, Sudhir K, Sievers RE, Zhu BQ, Sun YP, et al. Chronic dietary L-arginine prevents endothelial dysfunction secondary to environmental tobacco smoke in normocholesterolemic rabbits. Hypertension 1997; 29: 1186–1191.

    PubMed  CAS  CrossRef  Google Scholar 

  175. Zeiher AM, Schachinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation 1995; 92: 1094–1100.

    PubMed  CAS  CrossRef  Google Scholar 

  176. Thorne S, Mullen MJ, Clarkson P, Donald AE, Deanfield JE. Early endothelial dysfunction in adults at risk from atherosclerosis: different responses to L-arginine. J Am Coll Cardiol 1998; 32: 110–116.

    PubMed  CAS  CrossRef  Google Scholar 

  177. Watts GF, O’Brien SF, Silvester W, Millar JA. Impaired endothelium-dependent and independent dilatation of forearm resistance arteries in men with diet-treated non-insulin-dependent diabetes: role of dyslipidaemia. Clin Sci (Colch) 1996; 91: 567–573.

    CAS  Google Scholar 

  178. Nitenberg A, Ledoux S, Attali JR, Valensi P. [Response of the coronary arteries to cold test and flow velocity increase is improved by deferoxamine but not by L-arginine in diabetic patients]. Arch Mal Coeur Vaiss 1997; 90: 1037–1041.

    PubMed  CAS  Google Scholar 

  179. Pieper GM, Siebeneich W, Moore-Hilton G, Roza AM. Reversal by L-arginine of a dysfunctional arginine/nitric oxide pathway in the endothelium of the genetic diabetic BB rat. Diabetologia 1997; 40: 910–915.

    PubMed  CAS  CrossRef  Google Scholar 

  180. Mayhan WG, Patel KP, Sharpe GM. Effect of L-arginine on reactivity of hamster cheek pouch arterioles during diabetes mellitus. Int J Microcirc Clin Exp 1997; 17: 107–112.

    PubMed  CAS  CrossRef  Google Scholar 

  181. Pieper GM, Peltier BA. Amelioration by L-arginine of a dysfunctional arginine/nitric oxide pathway in diabetic endothelium. J Cardiovasc Pharmacol 1995; 25: 397–403.

    PubMed  CAS  CrossRef  Google Scholar 

  182. Pieper GM, Siebeneich W, Dondlinger LA. Short-term oral administration of L-arginine reverses defective endothelium-dependent relaxation and cGMP generation in diabetes. Eur J Pharmacol 1996; 317: 317–320.

    PubMed  CAS  CrossRef  Google Scholar 

  183. Mayhan WG, Didion SP, Patel KP. L-Arginine does not restore dilatation of the basilar artery during diabetes mellitus. J Cereb Blood Flow Metab 1996; 16: 500–506.

    PubMed  CAS  CrossRef  Google Scholar 

  184. Tesfamariam B, Cohen RA. Free radicals mediate endothelial cell dysfunction caused by elevated glucose. Am J Physiol 1992; 263: H321 - H326.

    PubMed  CAS  Google Scholar 

  185. Nitenberg A, Paycha F, Ledoux S, Sachs R, Attali JR, Valensi P. Coronary artery responses to physiological stimuli are improved by deferoxamine but not by L-arginine in non-insulin-dependent diabetic patients with angiographically normal coronary arteries and no other risk factors. Circulation 1998; 97: 736–743.

    PubMed  CAS  CrossRef  Google Scholar 

  186. MacAllister RJ, Calver AL, Collier J, Edwards CM, Herreros B, Nussey SS, et al. Vascular and hormonal responses to arginine: provision of substrate for nitric oxide or non-specific effect? Clin Sci (Colch) 1995; 89: 183–190.

    CAS  Google Scholar 

  187. Makimattila S, Mantysaari M, Groop PH, Summanen P, Virkamaki A, Schlenzka A, et al. Hyperreactivity to nitrovasodilators in forearm vasculature is related to autonomic dysfunction in insulin-dependent diabetes mellitus. Circulation 1997; 95: 618–625.

    PubMed  CAS  CrossRef  Google Scholar 

  188. Knock GA, McCarthy AL, Lowy C, Poston L. Association of gestational diabetes with abnormal maternal vascular endothelial function. Br J Obstet Gynaecol 1997; 104: 229–234.

    PubMed  CAS  CrossRef  Google Scholar 

  189. Giugliano D, Marfella R, Coppola L, Verrazzo G, Acampora R, Giunta R, et al. Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia. Circulation 1997; 95: 1783–1790.

    PubMed  CAS  CrossRef  Google Scholar 

  190. Paolisso G, Tagliamonte MR, Marfella R, Verrazzo G, D’ Onofrio F, Giugliano D. L-arginine but not D-arginine stimulates insulin-mediated glucose uptake. Metabolism 1997; 46: 1068–1073.

    PubMed  CAS  CrossRef  Google Scholar 

  191. Zeiher AM, Drexler H, Saurbier B, Just H. Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension. J Clin Invest 1993; 92: 652–662.

    PubMed  CAS  CrossRef  Google Scholar 

  192. Grisham MB, Miles AM. Effects of aminosalicylates and immunosuppressive agents on nitric oxide-dependent N-nitrosation reactions. Biochem Pharmacol 1994; 47: 1897–1902.

    PubMed  CAS  CrossRef  Google Scholar 

  193. Cosentino F, Katusic ZS. Tetrahydrobiopterin and dysfunction of endothelial nitric oxide synthase in coronary arteries. Circulation 1995; 91: 139–144.

    PubMed  CAS  CrossRef  Google Scholar 

  194. Schaffner A, Blau N, Schneemann M, Steurer J, Edgell CJ, Schoedon G. Tetrahydrobiopterin as another EDRF in man. Biochem Biophys Res Commun 1994; 205: 516–523.

    PubMed  CAS  CrossRef  Google Scholar 

  195. Balligand JL, Godfraind T. Endothelium-derived relaxing factor and muscle-derived relaxing factor in rat aorta: action of cyclosporin A. J Cardiovasc Pharmacol 1991; 17: S213 - S221.

    CAS  CrossRef  Google Scholar 

  196. Mathieu P, Carrier M, Dupuis J, Ryan J, Pelletier LC. L-arginine prevents cyclosporin A-induced pulmonary vascular dysfunction. Ann Thorac Sur 1997; 64: 414–420.

    CAS  CrossRef  Google Scholar 

  197. Gallego MJ, Lopez Fane A, Riesco A, Monton M, Grandes SM, Barat A, et al. Blockade of endothelium-dependent responses in conscious rats by cyclosporin A: effect of L-arginine Am J Physiol 1993; 264: H708 - H714.

    CAS  Google Scholar 

  198. Kim HS, Kim DH, Kang SW, Choi H, Lee HY, Han DS, et al. L-arginine restores suppressed acetylcholine-induced endothelium-dependent vascular relaxation in cyclosporine A-treated rats. Transplant Proc 1996; 28: 1372–1374.

    PubMed  CAS  Google Scholar 

  199. Harrison DG, Kurz MA, Quillen JE, Sellke FW, Mugge A. Normal and pathophysiologic considerations of endothelial regulation of vascular tone and their relevance to nitrate therapy. Am J Cardiol 1992; 70: 11B - 17B.

    PubMed  CAS  CrossRef  Google Scholar 

  200. Munzel T, Sayegh H, Freeman BA, Tarpey MM, Harrison DG. Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance. J Clin Invest 1995; 95: 187–194.

    PubMed  CAS  CrossRef  Google Scholar 

  201. Abou-Mohamed G, Kaesemeyer WH, Papapetropoulos A, Catravas JD, Caldwell RW. Nitroglycerin (NTG) but not sodium nitroprusside (SNP), increases aortic ring cGMP levels via an L-arginine dependent and L-NAME sensitive pathway. FASEB J 1995; 9: A327.

    Google Scholar 

  202. Kaesemeyer WH, Abou-Mohamed G, Crute TD, Caldwell RW. Nitrates supplemented with L-arginine for the reversal and treatment of nitrate tolerance: two case reports. Appl Cardiopulm Physiol 1997; 1–8.

    Google Scholar 

  203. Böger RH, Bode-Böger SM, Kienke S, Stan AC, Nafe R, Frolich JC. Dietary L-arginine decreases myointimal cell proliferation and vascular monocyte accumulation in cholesterol-fed rabbits. Atherosclerosis 1998; 136: 67–77.

    PubMed  CrossRef  Google Scholar 

  204. Cayatte AJ, Palacino JJ, Horten K, Cohen RA. Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscl Thromb 1994; 14: 753–759.

    PubMed  CAS  CrossRef  Google Scholar 

  205. Houston M, Chumley P, Radi R, Rubbo H, Freeman BA. Xanthine oxidase reaction with nitric oxide and peroxynitrite. Arch Biochem Biophys 1998; 355: 1–8.

    PubMed  CAS  CrossRef  Google Scholar 

  206. Pou S, Pou WS, Bredt DS, Snyder SH, Rosen GM. Generation of superoxide by purified brain nitric oxide synthase. J Biol Chem 1992; 267: 24173–24176.

    PubMed  CAS  Google Scholar 

  207. Klatt P, Pfeiffer S, List BM, Lehner D, Glatter O, Bachinger HP, et al. Characterization of hemedeficient neuronal nitric-oxide synthase reveals a role for heme in subunit dimerization and binding of the amino acid substrate and tetrahydrobiopterin. J Biol Chem 1996; 271: 7336–7442.

    PubMed  CAS  CrossRef  Google Scholar 

  208. Wang BY, Singer AH, Tsao PS, Drexler H, Kosek J, Cooke JP. Dietary arginine prevents atherogenesis in the coronary artery of the hypercholesterolemic rabbit. J Am Coll Cardiol 1994; 23: 452–458.

    PubMed  CAS  CrossRef  Google Scholar 

  209. Adams MR, Jessup W, Hailstones D, Celermajer DS. L-arginine reduces human monocyte adhesion to vascular endothelium and endothelial expression of cell adhesion molecules. Circulation 1997; 95: 662–668.

    PubMed  CAS  CrossRef  Google Scholar 

  210. Bath PM. The effect of nitric oxide-donating vasodilators on monocyte chemotaxis and intracellular cGMP concentrations in vitro. Eur J Clin Pharmacol 1993; 45: 53–58.

    PubMed  CAS  CrossRef  Google Scholar 

  211. Tsao PS, Buitrago R, Chan JR, Cooke JP. Fluid flow inhibits endothelial adhesiveness. Nitric oxide and transcriptional regulation of VCAM-1. Circulation 1996; 94: 1682–1689.

    PubMed  CAS  CrossRef  Google Scholar 

  212. Mami N, Offermann MK, Swerlick R, Kunsch C, Rosen CA, Ahmad M, et al. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest 1993; 92: 1866–1874.

    CrossRef  Google Scholar 

  213. Theilmeier G, Chan JR, Zalpour C, Anderson B, Wang BY, Wolf A, et al. Adhesiveness of mononuclear cells in hypercholesterolemic humans is normalized by dietary L-arginine. Arteriosc Thromb Vasc Biol 1997; 17: 3557–3564.

    CAS  CrossRef  Google Scholar 

  214. Ichiki K, Ikeda H, Haramaki N, Ueno T, Imaizumi T. Long-term smoking impairs platelet-derived nitric oxide release. Circulation 1996; 94: 3109–3114.

    PubMed  CAS  CrossRef  Google Scholar 

  215. Cadwgan TM, Benjamin N. Evidence for altered platelet nitric oxide synthesis in essential hypertension. J Hypertens 1993; 11: 417–420.

    PubMed  CAS  CrossRef  Google Scholar 

  216. Wolf A, Zalpour C, Theilmeier G, Wang BY, Ma A, Anderson B, et al. Dietary L-arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans. J Am Coll Cardiol 1997; 29: 479–485.

    PubMed  CAS  CrossRef  Google Scholar 

  217. 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: 1054–1061.

    PubMed  CAS  CrossRef  Google Scholar 

  218. Bode-Böger SM, Böger RH, Creutzig A, Tsikas D, Gutzki FM, Alexander K, et al. L-arginine infusion decreases peripheral arterial resistance and inhibits platelet aggregation in healthy subjects. Clin Sci (Colch) 1994; 87: 303–310.

    Google Scholar 

  219. Marietta M, Facchinetti F, Neri I, Piccinini F, Volpe A, Torelli G. L-arginine infusion decreases platelet aggregation through an intraplatelet nitric oxide release. Thromb Res 1997; 88: 229–235.

    PubMed  CAS  CrossRef  Google Scholar 

  220. Valiance P, Benjamin N, Collier J. The effect of endothelium-derived nitric oxide on ex vivo whole blood platelet aggregation in man. Eur J Clin Pharmacol 1992; 42: 37–41.

    CrossRef  Google Scholar 

  221. Bode-Böger SM, Boger RH, Galland A, Frolich JC. Differential inhibition of human platelet aggregation and thromboxane A2 formation by L-arginine in vivo and in vitro. Naunyn Schmiedebergs Arch Pharmacol 1998; 357: 143–150.

    PubMed  CrossRef  Google Scholar 

  222. Michel T, Smith TW. Nitric oxide synthases and cardiovascular signaling. Am Coll Cardiol 1993; 72: 33C - 38C.

    CAS  Google Scholar 

  223. Pohl U, Busse R. EDRF increases cyclic GMP in platelets during passage through the coronary vascular bed. Circ Res 1989; 65: 1798–1803.

    PubMed  CAS  CrossRef  Google Scholar 

  224. Mendez JD, Zarzoza E. Inhibition of platelet aggregation by L-arginine and polyamines in alloxan treated rats. Biochem Molec Biol Int 1997; 43: 311–318.

    PubMed  CAS  Google Scholar 

  225. Dambisya YM, Lee TL. A thromboelastography study on the in vitro effects of L-arginine and L-NGnitro arginine methyl ester on human whole blood coagulation and fibrinolysis. Blood Coag Fibrin 1996; 7: 678–683.

    CAS  CrossRef  Google Scholar 

  226. Udvardy M, Posan E, Palatka K, Altorjay I, Harsfalvi J. Effect of L-arginine on in vitro plasmingeneration and fibrinogenolysis. Thromb Res 1997; 87: 75–82.

    PubMed  CAS  CrossRef  Google Scholar 

  227. Gryglewski RJ, Grodzinska L, Kostka-Trabka E, Korbut R, Bieroon K, Goszcz A, et al. Treatment with L-arginine is likely to stimulate generation of nitric oxide in patients with peripheral arterial obstructive disease. Wien Klin Wochenschr 1996; 108: 111–116.

    PubMed  CAS  Google Scholar 

  228. Marfella R, Acampora R, Verrazzo G, Ziccardi P, De Rosa N, Giunta R, et al. Metformin improves hemodynamic and rheological responses to L-arginine in NIDDM patients. Diabetes Care 1996; 19: 934–939.

    PubMed  CAS  CrossRef  Google Scholar 

  229. Lou H, Kodama T, Wang YN, Katz N, Ramwell P, Foegh ML. L-arginine prevents heart transplant arteriosclerosis by modulating the vascular cell proliferative response to insulin-like growth factor-I and interleukin-6 J Heart Lung Transplant 1996; 15: 1248–1257.

    CAS  Google Scholar 

  230. Katan MB, Vroomen LH, Hermus RJ. Reduction of casein-induced hypercholesterolaemia and atherosclerosis in rabbits and rats by dietary glycine, arginine and alanine. Atherosclerosis 1982; 43: 381–391.

    PubMed  CAS  CrossRef  Google Scholar 

  231. Hamon M, Vallet B, Bauters C, Wernert N, McFadden EP, Lablanche JM, et al. Long-term oral administration of L-arginine reduces intimal thickening and enhances neoendothelium-dependent acetylcholine-induced relaxation after arterial injury. Circulation 1994; 90: 1357–1362.

    PubMed  CAS  CrossRef  Google Scholar 

  232. Wang BY, Candipan RC, Arjomandi M, Hsiun PT, Tsao PS, Cooke JP. Arginine restores nitric oxide activity and inhibits monocyte accumulation after vascular injury in hypercholesterolemic rabbits. J Am Coll Cardiol 1996; 28: 1573–1579.

    PubMed  CAS  CrossRef  Google Scholar 

  233. Davies MG, Kim JH, Dalen H, Makhoul RG, Svendsen E, Hagen PO. Reduction of experimental vein graft intimal hyperplasia and preservation of nitric oxide-mediated relaxation by the nitric oxide precursor L-arginine Surgery 1994; 116: 557–568.

    CAS  Google Scholar 

  234. Okazaki J, Komori K, Kawasaki K, Eguchi D, Ishida M, Sugimachi K. L-arginine inhibits smooth muscle cell proliferation of vein graft intimai thickness in hypercholesterolemic rabbits. Cardiovasc Res 1997; 36: 429–436.

    PubMed  CAS  CrossRef  Google Scholar 

  235. Dattilo JB, Dattilo MP, Crane JT, Yager DR, Makhoul RG. The nitric oxide precursor L-arginine reduces expression of hyaluronan synthase in experimental vein bypass grafts. J Surg Res 1998; 74: 39–42.

    PubMed  CAS  CrossRef  Google Scholar 

  236. Pipili-Synetos E, Sakkoula E, Maragoudakis ME. Nitric oxide is involved in the regulation of angiogenesis. Br J Pharmacol 1993; 108: 855–857.

    PubMed  CAS  CrossRef  Google Scholar 

  237. Papapetropoulos A, Garcia-Cardena G, Madri JA, Sessa WC. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 1997; 100: 3131–3139.

    PubMed  CAS  CrossRef  Google Scholar 

  238. van der Zee R, Murohara T, Luo Z, Zollmann F, Passeri J, Lekutat C, et al. Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium. Circulation 1997; 95: 1030–1037.

    PubMed  CrossRef  Google Scholar 

  239. Murohara T, Asahara T, Silver M, Bauters C, Masuda H, Kalka C, et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest 1998; 101: 2567–2578.

    PubMed  CAS  CrossRef  Google Scholar 

  240. Quyyumi AA, Dakak N, Andrews NP, Husain S, Arora S, Gilligan DM, et al. Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis. J Clin Invest 1995; 95: 1747–1755.

    PubMed  CAS  CrossRef  Google Scholar 

  241. Hirooka Y, Egashira K, Imaizumi T, Tagawa T, Kai H, Sugimachi M, et al. Effect of L-arginine on acetylcholine-induced endothelium-dependent vasodilation differs between the coronary and forearm vasculatures in humans. J Am Coll Cardiol 1994; 24: 948–955.

    PubMed  CAS  CrossRef  Google Scholar 

  242. Otsuji S, Nakajima O, Waku S, Kojima S, Hosokawa H, Kinoshita I, et al. Attenuation of acetylcholine-induced vasoconstriction by L-arginine is related to the progression of atherosclerosis. Am Heart J 1995; 129: 1094–1100.

    PubMed  CAS  CrossRef  Google Scholar 

  243. Lekakis J, Papamichael C, Agrios N, Vemmos A, Voutsas S, Stamatelopoulos S, et al. Peripheral vascular endothelial dysfunction in patients with microvascular angina pectoris. J Am Coll Cardiol 1997; 29: 175A.

    Google Scholar 

  244. Egashira K, Hirooka Y, Kuga T, Mohri M, Takeshita A. Effects of L-arginine supplementation on endothelium-dependent coronary vasodilation in patients with angina pectoris and normal coronary arteriograms. Circulation 1996; 94: 130–134.

    PubMed  CAS  CrossRef  Google Scholar 

  245. 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: 2123–2128.

    PubMed  CAS  CrossRef  Google Scholar 

  246. Ceremuzynski L, Chamiec T, Herbaczynska-Cedro K. Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris. Am J Cardiol 1997; 80: 331–333.

    PubMed  CAS  CrossRef  Google Scholar 

  247. Ceremuzynski L, Tomasz C, Herbaczynska-Cedro K. L-arginine improves exercise capacity in patients with stable angina. J Am Coll Cardiol 1997; 29: 157A.

    Google Scholar 

  248. Böger R, Bode-Böger SM, Thiele W, Alexander K, Frolich JC. Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. Circulation 1998; 95: 2068–2074.

    CrossRef  Google Scholar 

  249. Mehta S, Stewart DJ, Levy RD. The hypotensive effect of L-arginine is associated with increased expired nitric oxide in humans. Chest 1996; 109: 1550–1555.

    PubMed  CAS  CrossRef  Google Scholar 

  250. Bijlsma JA, Rabelink AJ, Kaasjager KA, Koomans HA. L-arginine does not prevent the renal effects of endothelin in humans. J Am Soc Nephrol 1995; 5: 1508–1516.

    PubMed  CAS  Google Scholar 

  251. Hishikawa K, Nakaki T, Tsuda M, Esumi H, Ohshima H, Suzuki H, et al. Effect of systemic L-arginine administration on hemodynamics and nitric oxide release in man. Jpn Heart J 1992; 33: 41–48.

    PubMed  CAS  CrossRef  Google Scholar 

  252. Giugliano D, Marfella R, Verrazzo G, Acampora R, Nappo F, Ziccardi P, et al. L-arginine for testing endothelium-dependent vascular functions in health and disease. Am J Physiol 1997; 273: E606 - E612.

    PubMed  CAS  Google Scholar 

  253. Harima A, Shimizu H, Takagi H. Analgesic effect of L-arginine in patients with persistent pain. Eur Neuropsychopharmacol 1991; 1: 529–533.

    PubMed  CAS  CrossRef  Google Scholar 

  254. Nakaki T, Hishikawa K, Suzuki H, Saruta T, Kato R. L-arginine-induced hypotension. Lancet 1990; 336: 696.

    PubMed  CAS  CrossRef  Google Scholar 

  255. Kanno K, Hirata Y, Emori T, Ohta K, Eguchi S, Imai T, et al. L-arginine infusion induces hypotension and diuresis/natriuresis with concomitant increased urinary excretion of nitrite/nitrate and cyclic GMP in humans. Clin Exp Pharmacol Phys 1992; 19: 619–625.

    CAS  CrossRef  Google Scholar 

  256. Hishikawa K, Nakaki T, Suzuki H, Kato R, Saruta T. Role of L-arginine-nitric oxide pathway in hypertension. J Hypertens 1993; 11: 639–645.

    PubMed  CAS  CrossRef  Google Scholar 

  257. Hishikawa K, Nakaki T, Suzuki H, Saruta T, Kato R. L-arginine-induced hypotension. Lancet 1991; 337: 683, 684.

    Google Scholar 

  258. Laghi Pasini F, Frigerio C, Blardi P, Domini L, De Giorgi L, Borgogni G, et al. Evidence of an adenosine-dependent mechanism in the hypotensive effect of L-arginine in man. Clin Exp Pharmacol Physiol 1995; 22: 254–259.

    CrossRef  Google Scholar 

  259. Petros AJ, Hewlett AM, Bogle RG, Pearson JD. L-arginine-induced hypotension. Lancet 1991; 337: 1044, 1045.

    Google Scholar 

  260. Chen PY, St. John PL, Kirk KA, Abrahamson DR, Sanders PW. Hypertensive nephrosclerosis in the Dahl/Rapp rat. Initial sites of injury and effect of dietary L-arginine supplementation. Lab Invest 1993; 68: 174–184.

    PubMed  CAS  Google Scholar 

  261. Chen PY, Sanders PW. L-arginine abrogates salt-sensitive hypertension in Dahl/Rapp rats. J Clin Invest 1991; 88: 1559–1567.

    PubMed  CAS  CrossRef  Google Scholar 

  262. Turner SW, Wen C, Li M, Whitworth JA. L-arginine prevents corticotropin-induced increases in blood pressure in the rat. Hypertension 1996; 27: 184–189.

    PubMed  CAS  CrossRef  Google Scholar 

  263. Laurant P, Demolombe B, Berthelot. Dietary L-arginine attenuates blood pressure in mineralocorticoid-salt hypertensive rats. Clin Exp Hypertens 1995; 17: 1009–1024.

    PubMed  CAS  CrossRef  Google Scholar 

  264. Matsuoka H, Nakata M, Kohno K, Koga Y, Nomura G, Toshima A. Chronic L-arginine administration attenuates cardiac hypertrophy in spontaneously hypertensive rats. Hypertension 1996; 27: 14–18.

    PubMed  CAS  CrossRef  Google Scholar 

  265. Tomohiro A, Kimura S, He H, Fujisawa Y, Nishiyama A, Kiyomoto K, et al. Regional blood flow in Dahl-Iwai salt-sensitive rats and the effects of dietary L-arginine supplementation. Am J Physiol 1997; 272: R1013 - R1019.

    PubMed  CAS  Google Scholar 

  266. Li M, Fraser T, Wang J, Whitworth JA. Dexamethasone-induced hypertension in the rat: effects of L-arginine. Clin Exp Pharmacol Physiol 1997; 24: 730–732.

    PubMed  CAS  CrossRef  Google Scholar 

  267. Helmbrecht GD, Farhat MY, Lochbaum L, Brown HE, Yadgarova KT, Eglinton GS, et al. L-arginine reverses the adverse pregnancy changes induced by nitric oxide synthase inhibition in the rat. Am J Obstet Gynecol 1996; 175: 800–805.

    PubMed  CAS  CrossRef  Google Scholar 

  268. Pucci ML, Dick LB, Miller KB, Smith CJ, Nasjletti A. Enhanced responses to L-arginine in aortic rings from rats with angiotensin-dependent hypertension. J Pharmacol Exp Therap 1995; 274: 1–7.

    CAS  Google Scholar 

  269. Ding Y, Vaziri ND, Gonick HC. Lead-induced hypertension. II. Response to sequential infusions of L-arginine, superoxide dismutase, and nitroprusside. Environ Res 1998; 76: 107–113.

    PubMed  CAS  CrossRef  Google Scholar 

  270. Jimbo M, Suzuki H, Ichikawa M, Kumagai K, Nishizawa M, Saruta T. Role of nitric oxide in regulation of baroreceptor reflex. J Auton Nerve Sys 1994; 50: 209–219.

    CAS  CrossRef  Google Scholar 

  271. Higashi Y, Oshima T, Sasaki N, Ishioka N, Nakano Y, Ozono R, et al. Relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension. Hypertension 1997; 29: 280–285.

    PubMed  CAS  CrossRef  Google Scholar 

  272. Matsuoka H, Itoh S, Kimoto M, Kohno K, Tamai O, Wada Y, et al. Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension. Hypertension 1997; 29: 242–247.

    PubMed  CAS  CrossRef  Google Scholar 

  273. Haulica I, Cosovanu A, Ungureanu G, Zaharia D, Baltatu O, Boisteanu D. Cardiovascular effects of L-arginine as physiological precursor of nitric oxide. Rom J Int Med 1994; 32: 195–201.

    CAS  Google Scholar 

  274. Pedrinelli R, Ebel M, Catapano G, Dell’Orno G, Ducci M, Del Chicca M, et al. Pressor, renal and endocrine effects of L-arginine in essential hypertensives. Eur J Clin Pharmacol 1995; 48: 195–201.

    PubMed  CAS  CrossRef  Google Scholar 

  275. Wideman RF Jr, Kirby YK, Ismail M, Bottje WG, Moore RW, Vardeman RC. Supplemental L-arginine attenuates pulmonary hypertension syndrome (ascites) in broilers. Poult Sci 1995; 74: 323–330.

    PubMed  CAS  CrossRef  Google Scholar 

  276. Mitani Y, Maruyama K, Sakurai M. Prolonged administration of L-arginine ameliorates chronic pulmonary hypertension and pulmonary vascular remodeling in rats. Circulation 1997; 96: 689–697.

    PubMed  CAS  CrossRef  Google Scholar 

  277. Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 1995; 333: 214–221.

    PubMed  CAS  CrossRef  Google Scholar 

  278. Vosatka RJ, Kashyap S, Trifiletti RR. Arginine deficiency accompanies persistent pulmonary hypertension of the newborn. Biol Neonate 1994; 66: 65–70.

    PubMed  CAS  CrossRef  Google Scholar 

  279. Castillo L, DeRojas-Walker T, Yu YM, Sanchez M, Chapman TE, Shannon D, et al. Whole body arginine metabolism and nitric oxide synthesis in newborns with persistent pulmonary hypertension. Pediatr Res 1995; 38: 17–24.

    PubMed  CAS  CrossRef  Google Scholar 

  280. Stewart DJ. Endothelial dysfunction in pulmonary vascular disorders. Arzneimittel-Forschung 1994; 44: 451–454.

    PubMed  CAS  Google Scholar 

  281. Baudouin SV, Bath P, Martin JF, Du Bois R, Evans TW. L-arginine infusion has no effect on systemic haemodynamics in normal volunteers, or systemic and pulmonary haemodynamics in patients with elevated pulmonary vascular resistance. Br J Clin Pharmacol 1993; 36: 45–49.

    PubMed  CAS  CrossRef  Google Scholar 

  282. Katz SD, Krum H, Khan T, Knecht M. Exercise-induced vasodilation in forearm circulation of normal subjects and patients with congestive heart failure: role of endothelium-derived nitric oxide. J Am Coll Cardiol 1996; 28: 585–590.

    PubMed  CAS  CrossRef  Google Scholar 

  283. Takeshita A, Hirooka Y, Imaizumi T. Role of endothelium in control of forearm blood flow in patients with heart failure. J Cardiac Fail 1996; 2: 5209–5215.

    CrossRef  Google Scholar 

  284. Drexler H, Hayoz D, Munzel T, Hornig B, Just H, Brunner HR, et al. Endothelial function in chronic congestive heart failure. Am J Cardiol 1992; 69: 1596–1601.

    PubMed  CAS  CrossRef  Google Scholar 

  285. Koifman B, Wollman Y, Bogomolny N, Chernichowsky T, Finkelstein A, Per G, et al. Improvement of cardiac performance by intravenous infusion of L-arginine in patients with moderate congestive heart failure. J Am Coll Cardiol 1995; 26: 1251–1256.

    PubMed  CAS  CrossRef  Google Scholar 

  286. Howes TQ, Keilty SE, Maskrey VL, Deane CR, Baudouin SV, Moxham J. Effect of L-arginine on renal blood flow in normal subjects and patients with hypoxic chronic obstructive pulmonary disease. Thorax 1996; 51: 516–519.

    PubMed  CAS  CrossRef  Google Scholar 

  287. Morikawa E, Moskowitz MA, Huang Z, Yoshida T, Irikura K, Dalkara T. L-arginine infusion promotes nitric oxide-dependent vasodilation, increases regional cerebral blood flow, and reduces infarction volume in the rat. Stroke 1994; 25: 429–435.

    PubMed  CAS  CrossRef  Google Scholar 

  288. Sadoshima S, Nagao T, Okada Y, Fujii K, Ibayashi S, Fujishima M. L-arginine ameliorates recirculation and metabolic derangement in brain ischemia in hypertensive rats. Brain Res 1997; 744: 246–252.

    PubMed  CAS  CrossRef  Google Scholar 

  289. DeWitt DS, Smith TG, Deyo DJ, Miller KR, Uchida T, Prough DS. L-arginine and superoxide dismutase prevent or reverse cerebral hypoperfusion after fluid-percussion traumatic brain injury. J Neurotrauma 1997; 14: 223–233.

    PubMed  CAS  CrossRef  Google Scholar 

  290. Prado R, Watson BD, Zhao W, Yao H, Busto R, Dietrich WD, et al. L-arginine does not improve cortical perfusion or histopathological outcome in spontaneously hypertensive rats subjected to distal middle cerebral artery photothrombotic occlusion. J Cereb Blood Flow Metab 1996; 16: 612–622.

    PubMed  CAS  CrossRef  Google Scholar 

  291. Kirsch JR, Bhardwaj A, Martin LJ, Hanley DF, Traystman RJ. Neither L-arginine nor L-NAME affects neurological outcome after global ischemia in cats. Stroke 1997; 28: 2259–2264.

    PubMed  CAS  CrossRef  Google Scholar 

  292. Nakagomi T, Kanemitsu H, Takagi K, Morikawa E, Kirino T, Tamura A. Effect of L-arginine and NGnitro-L-arginine on delayed neuronal death in the gerbil hippocampus. Neurol Res 1997; 19: 426–430.

    PubMed  CAS  Google Scholar 

  293. Huang Z, Huang PL, Ma J, Meng W, Ayata C, Fishman MC, et al. Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine. J Cereb Blood Flow Metab 1996; 16: 981–987.

    PubMed  CAS  CrossRef  Google Scholar 

  294. Samdani AF, Dawson TM, Dawson VL. Nitric oxide synthase in models of focal ischemia. Stroke 1997; 28: 1283–1288.

    PubMed  CAS  CrossRef  Google Scholar 

  295. Wang QD, Morcos E, Wiklund P, Pernow J. L-arginine enhances functional recovery and Ca2+dependent nitric oxide synthase activity after ischemia and reperfusion in the rat heart. J Cardiovasc Pharmacol 1997; 29: 291–296.

    PubMed  CAS  CrossRef  Google Scholar 

  296. Wang P, Zweier JL. Ischemic preconditioning decreases nitric oxide (NO) formation and NO mediated injury in the postischemic heart. Circulation 1997; 96: I - 72.

    Google Scholar 

  297. Li XS, Uriuda Y, Wang QD, Norlander R, Sjoquist PO, Pernow J. Role of L-arginine in preventing myocardial and endothelial injury following ischaemia/reperfusion in the rat isolated heart. Acta Physiol Scand 1996; 156: 37–44.

    PubMed  CAS  CrossRef  Google Scholar 

  298. Brunner F, Leonhard B, Kukovetz WR, Mayer B. Role of endothelin, nitric oxide and L-arginine release in ischaemia/reperfusion injury of rat heart. Cardiovasc Res 1997; 36: 60–66.

    PubMed  CAS  CrossRef  Google Scholar 

  299. Weyrich AS, Ma XL, Lefer AM. The role of L-arginine in ameliorating reperfusion injury after myocardial ischemia in the cat. Circulation 1992; 86: 279–288.

    PubMed  CAS  CrossRef  Google Scholar 

  300. Nakanishi K, Vinten-Johansen J, Lefer DJ, Zhao Z, Fowler WC, McGee DS, et al. Intracoronary L-arginine during reperfusion improves endothelial function and reduces infarct size. Am J Physiol 1992; 263: H1650 - H1658.

    PubMed  CAS  Google Scholar 

  301. Takeuchi K, Takashima K, Suzuki S, Fukui K. [Basic amino acid, L-arginine aggravates ischemiareperfusion injury]. Nippon Kyobu Geka Gakkai Zasshi 1996; 44: 155–161.

    PubMed  CAS  Google Scholar 

  302. Fei L, Baron AD, Henry DP, Zipes DP. Intrapericardial delivery of L-arginine reduces the increased severity of ventricular arrhythmias during sympathetic stimulation in dogs with acute coronary occlusion: nitric oxide modulates sympathetic effects on ventricular electrophysiological properties. Circulation 1997; 96: 4044–4049.

    PubMed  CAS  CrossRef  Google Scholar 

  303. Burra P, Ferraresso M, Cadrobbi R, Calabrese F, Crdin R, Parnigotto A, et al. Effect of L-arginine and oligotide on liver ischemia-reperfusion injury. Transplant Proc 1997; 29: 2992–2993.

    PubMed  CAS  CrossRef  Google Scholar 

  304. Shiraishi M, Kusano T, Aihara T, Ikeda Y, Koyama Y, Muto Y. Protection against hepatic ischemia/ reperfusion injury by exogenous L-arginine. Transplant Proc 1996; 28: 1887–1888.

    PubMed  CAS  Google Scholar 

  305. Calabrese F, Valente M, Pettenazzo E, Ferraresso M, Burra P, Cadrobbi R, et al. The protective effects of L-arginine after liver ischaemia/reperfusion injury in a pig model. J Pathol 1997; 183: 477–485.

    PubMed  CAS  CrossRef  Google Scholar 

  306. Shiraishi M, Hiroyasu S, Nagahama M, Miyaguni T, Higa T, Tomori H, et al. Role of exogenous L-arginine in hepatic ischemia-reperfusion injury. J Surg Res 1997; 69: 429–434.

    PubMed  CAS  CrossRef  Google Scholar 

  307. Hiramatsu T, Forbess JM, Miura T, Roth SJ, Cioffi MA, Mayer JE Jr. Effects of endothelin-1 and L-arginine after cold ischemia in lamb hearts. Ann Thorac Surg 1997; 61: 36–40.

    CrossRef  Google Scholar 

  308. Duke T, South M, Stewart A. Altered activation of the L-arginine nitric oxide pathway during and after cardiopulmonary bypass. Perfusion 1997; 12: 405–410.

    PubMed  CAS  Google Scholar 

  309. Stowe DF, Boban M, Roerig DL, Chang D, Palmisano BW, Bosnjak ZJ. Effects of L-arginine and N omega-nitro-L-arginine methyl ester on cardiac perfusion and function after 1-day cold preservation of isolated hearts. Circulation 1997; 95: 1623–1634.

    CAS  Google Scholar 

  310. Hiramatsu T, Forbess JM, Miura T, Mayer JE Jr. Effect of L-arginine cardioplegia on recovery of neonatal lamb hearts after 2 hours of cold ischemia. Ann Thorac Surg 1995; 60: 1187–1192.

    PubMed  CAS  CrossRef  Google Scholar 

  311. Hiramatsu T, Forbess JM, Miura T, Mayer JE Jr. Effects of L-arginine and L-nitro-arginine methyl ester on recovery of neonatal lamb hearts after cold ischemia. Evidence for an important role of endothelial production of nitric oxide. J Thorac Cardiovasc Surg 1995; 109: 81–86.

    PubMed  CAS  CrossRef  Google Scholar 

  312. Szabo G, Bahrle S, Dengler TJ, Batkai S, Vahl CF, Hagl S. [Reducing perfusion damage after heart transplantation with the nitric oxide donor L-arginine]. Langenbecks Arch Chir Supplement Kongressbd 1997; 114: 7–10.

    Google Scholar 

  313. Normandin L, Herve P, Brink C, Chapelier AR, Dartevelle PG, Mazmanian GM. L-arginine and pentoxifylline attenuate endothelial dysfunction after lung reperfusion injury in the rabbit. The Paris-Sud University Lung Transplant Group. Ann Thorac Surg 1995; 60: 646–650.

    PubMed  CAS  CrossRef  Google Scholar 

  314. Um SC, Suzuki S, Toyokuni S, Kim BM, Tanaka T, Hiai H, et al. Involvement of nitric oxide in survival of random pattern skin flap. Plast Reconstr Surg 1998; 101: 785–792.

    PubMed  CAS  CrossRef  Google Scholar 

  315. Cordeiro PG, Mastorakos DP, Hu QY, Kirschner RE. The protective effect of L-arginine on ischemiareperfusion injury in rat skin flaps. Plastic Reconst Surg 1997; 100: 1227–1233.

    CAS  CrossRef  Google Scholar 

  316. Ercocen AR, Apaydin I, Emiroglu M, Gultan SM, Ergun H, Yormuk E. The effects of L-arginine and iloprost on the viability of random skin flaps in rats. Scand J Plast Reconstr Surg Hand Surg 1998; 32: 19–25.

    PubMed  CAS  CrossRef  Google Scholar 

  317. Walls CM, Gregory CR, Beck LS, Cooke JP, Griffey SM, Kass PH. Effects of growth factors and L-arginine on ischemic skin flaps in rats. Vet Surg 1995; 24: 484–491.

    PubMed  CAS  CrossRef  Google Scholar 

  318. Melis MR, Argiolas A. Role of central nitric oxide in the control of penile erection and yawning. Prog Neuropsychopharmacol Biol Psych 1997; 21: 899–922.

    CAS  CrossRef  Google Scholar 

  319. Garban H, Vernet D, Freedman A, Rajfer J, Gonzalez-Cadavid N. Effect of aging on nitric oxide-mediated penile erection in rats. Am J Physiol 1995; 268: H467 - H475.

    PubMed  CAS  Google Scholar 

  320. Xie Y, Garban H, Ng C, Rajfer J, Gonzalez-Cadavid NF. Effect of long-term passive smoking on erectile function and penile nitric oxide synthase in the rat. J Urol 1997; 157: 1121–1126.

    PubMed  CAS  CrossRef  Google Scholar 

  321. Vernet D, Cai L, Garban H, Babbitt ML, Murray FT, Rajfer J, et al. Reduction of penile nitric oxide synthase in diabetic BB/WORdp (type I) and BBZ/WORdp (type II) rats with erectile dysfunction. Endocrinology 1995; 136: 5709–5717.

    PubMed  CAS  CrossRef  Google Scholar 

  322. Kim YC, Davies MG, Hagen PO, Carson CC. Experimental evidence for endothelium dependent relaxation and neuronal nitric oxide in corpus cavernosum. Yonsei Med J 1994; 35: 308–313.

    PubMed  CAS  Google Scholar 

  323. Penson DF, Ng C, Rajfer J, Gonzalez-Cadavid NF. Adrenal control of erectile function and nitric oxide synthase in the rat penis. Endocrinology 1997; 138: 3925–3932.

    PubMed  CAS  CrossRef  Google Scholar 

  324. Kimura K, Takahashi M, Naroda T, Iriguchi H, Miyamoto T, Kawanishi Y, et al. [The relaxation of human corpus cavernosum caused by nitric oxide]. Nippon Hinyokika Gakkai Zasshi 1993; 84: 1660–1664.

    PubMed  CAS  Google Scholar 

  325. Simonsen U, Prieto D, Delgado JA, Hernandez M, Resel L, Saenz de Tejada I, et al. Nitric oxide is involved in the inhibitory neurotransmission and endothelium-dependent relaxations of human small penile arteries. Clin Sci (Colch) 1997; 92: 269–275.

    CAS  Google Scholar 

  326. Benelli A, Bertolini A, Poggioli R, Cavazzuti E, Calza L, Giardino L, et al. Nitric oxide is involved in male sexual behavior of rats. Eur J Pharmacol 1995; 294: 505–510.

    PubMed  CAS  CrossRef  Google Scholar 

  327. Luscher TF, Bock HA. The endothelial L-arginine/nitric oxide pathway and the renal circulation. Klin Wochenschr 1991; 69: 603–609.

    PubMed  CAS  CrossRef  Google Scholar 

  328. De Nicola L, Minutolo R, Bellizzi V, Andreucci M, La Verde A, Cianciaruso B. Enhancement of nitric oxide synthesis by L-arginine supplementation in renal disease: is it good or bad? Miner Electrolyte Metab 1997; 23: 144–150.

    PubMed  Google Scholar 

  329. Katoh T, Takahashi K, Klahr S, Reyes AA, Badr KF. Dietary supplementation with L-arginine ameliorates glomerular hypertension in rats with subtotal nephrectomy. J Am Soc Nephrol 1994; 4: 1690–1694.

    PubMed  CAS  Google Scholar 

  330. Ashab I, Peer G, Blum M, Wollman Y, Chernihovsky T, Hassner A, et al. Oral administration of L-arginine and captopril in rats prevents chronic renal failure by nitric oxide production. Kidney Int 1995; 47: 1515–1521.

    PubMed  CAS  CrossRef  Google Scholar 

  331. Wakabayashi Y, Kikawada R. Effect of L-arginine on myoglobin-induced acute renal failure in the rabbit. Am J Physiol 1996; 270: F784 - F789.

    PubMed  CAS  Google Scholar 

  332. De Nicola L, Thomson SC, Wead LM, Brown MR, Gabbai FB. Arginine feeding modifies cyclosporine nephrotoxicity in rats. J Clin Invest 1993; 92: 1859–1865.

    PubMed  CrossRef  Google Scholar 

  333. Kumagai K, Suzuki H, Ichikawa M, Jimbo M, Murakami M, Ryuzaki M, et al. Nitric oxide increases renal blood flow by interacting with the sympathetic nervous system. Hypertension 1994; 24: 220–226.

    PubMed  CAS  CrossRef  Google Scholar 

  334. Aiello S, Noris M, Remuzzi G. Nitric oxide synthesis and L-arginine in uremia. Miner Electrolyte Metab 1997; 23: 151–156.

    PubMed  CAS  Google Scholar 

  335. Reyes AA, Klahr S. Dietary supplementation of L-arginine ameliorates renal hypertrophy in rats fed a high-protein diet. Proc Soc Exp Biol Med 1994; 206: 157–161.

    PubMed  CAS  Google Scholar 

  336. Thomas SE, Andoh TF, Pichler RH, Shankland SJ, Couser WG, Bennett WM, et al. Accelerated apoptosis characterizes cyclosporine-associated interstitial fibrosis. Kidney Int 1998; 53: 897–908.

    PubMed  CAS  CrossRef  Google Scholar 

  337. Yang CW, Kim YS, Kim J, Kim YO, Min SY, Choi EJ, et al. Oral supplementation of L-arginine prevents chronic cyclosporine nephrotoxicity in rats. Exp Nephrol 1998; 6: 50–56.

    PubMed  CAS  CrossRef  Google Scholar 

  338. Assis SM, Monteiro JL, Seguro AC. L-Arginine and allopurinol protect against cyclosporine nephrotoxicity. Transplantation 1997; 63: 1070–1073.

    PubMed  CAS  CrossRef  Google Scholar 

  339. MacAllister RJ, Rambausek MH, Vallance P, Williams D, Hoffmann KH, Ritz E. Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure. Nephr Dialys Transplant 1996; 11: 2449–2452.

    CAS  CrossRef  Google Scholar 

  340. Andres A, Morales JM, Praga M, Campo C, Lahera V, Garcia-Robles R, et al. L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients. Nephrol Dialys Transplant 1997; 12: 1437–1440.

    CAS  CrossRef  Google Scholar 

  341. Creager MA, Halperin JL, Coffman, JD. Vasospastic diseases. In: Loscalzo J, Creager MA, Dzau VJ, eds. The Textbook of Vascular Medicine. Little Brown, Boston, 1992, pp. 975–1010.

    Google Scholar 

  342. Coffman JD, Davies WT. Vasospastic disease: a review. Prog Cardiovasc Dis 1975; 18: 123–146.

    PubMed  CAS  CrossRef  Google Scholar 

  343. Robertson D, Oates JA. Variant angina and Raynaud’s phenomenon. Lancet 1978; 1: 452.

    PubMed  CAS  CrossRef  Google Scholar 

  344. Flavahan NA Human postjunctional alpha 1 and alpha 2-adrenoceptors: differential distribution in arteries of the limbs. J Pharmacol Exp Ther 1986;241:361–365.

    Google Scholar 

  345. Moulds RF, Iwanov V, Medcalf RL. The effects of platlet-derived contractile agents on human digital arteries. Clin Sci 1984; 66: 443–451.

    PubMed  CAS  Google Scholar 

  346. Coffman JD, Cohen RA. Serotoninergic vasoconstriction in human fingers during reflex sympathetic responses to cooling. Am J Physiol 1988; 254: H889 - H893.

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2000 Springer Science+Business Media New York

About this chapter

Cite this chapter

Maxwell, A.J., Cooke, J.P. (2000). L-Arginine. In: Loscalzo, J., Vita, J.A. (eds) Nitric Oxide and the Cardiovascular System. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-002-5_30

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-002-5_30

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-101-1

  • Online ISBN: 978-1-59259-002-5

  • eBook Packages: Springer Book Archive