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Pros and cons of L-arginine supplementation in disease

Published online by Cambridge University Press:  14 December 2007

Yvonne L. J. Vissers
Affiliation:
Department of Surgery, Maastricht University, PO Box 616, NL-6200 MD Maastricht, The Netherlands
Iris B. J. G. Debats
Affiliation:
Department of Plastic Surgery, Maastricht University, Maastricht, The Netherlands
Yvette C. Luiking
Affiliation:
Department of Surgery, Maastricht University, PO Box 616, NL-6200 MD Maastricht, The Netherlands
Rajiv Jalan
Affiliation:
Department of Hepatology, Royal Free and University College Medical School, London, UK
René R. W. J. van der Hulst
Affiliation:
Department of Plastic Surgery, Maastricht University, Maastricht, The Netherlands
Cornelis H. C. Dejong
Affiliation:
Department of Surgery, Maastricht University, PO Box 616, NL-6200 MD Maastricht, The Netherlands
Nicolaas E. P. Deutz*
Affiliation:
Department of Surgery, Maastricht University, PO Box 616, NL-6200 MD Maastricht, The Netherlands
*
*Corresponding author: Dr Nicolaas E. P. Deutz, fax +31 43 3882126, email nep.deutz@ah.unimaas.nl
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Abstract

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The amino acid arginine and one of its metabolites NO have gathered broad attention in the last decade. Although arginine is regarded as a conditionally essential amino acid in disease, L-arginine supplementation in severe illness has not found its way into clinical practice. This might be due to the invalid interpretation of results from studies with immune-enhancing diets containing L-arginine amongst other pharmaconutrients. However, not much attention is given to research using L-arginine as a monotherapy and the possibility of the alternative hypothesis: that L-arginine supplementation is beneficial in disease. The present review will discuss data from studies in healthy and diseased animals and patients with monotherapy of L-arginine to come to an objective overview of positive and negative aspects of L-arginine supplementation in disease with special emphasis on sepsis, cancer, liver failure and wound healing.

Type
research-article
Copyright
Copyright © The Authors 2004

References

Adamik, B, Kubler-Kielb, J, Golebiowska, B, Gamian, A, & Kubler, A (2000) Effect of sepsis and cardiac surgery with cardiopulmonary bypass on plasma level of nitric oxide metabolites, neopterin, and procalcitonin: correlation with mortality and postoperative complications. Intensive Care Medicine 26, 12591267.CrossRefGoogle ScholarPubMed
Adawi, D, Kasravi, FB, Molin, G, & Jeppsson, B (1996) Oral arginine supplementation in acute liver injury. Nutrition 12, 529533.CrossRefGoogle ScholarPubMed
Aggarwal, S, Kang, Y, Freeman, JA, Fortunato, FL, & Pinsky, MR (1987) Postreperfusion syndrome: cardiovascular collapse following hepatic reperfusion during liver transplantation. Transplantation Proceedings 19, 5455.Google ScholarPubMed
Aggarwal, S, Kang, Y, Freeman, JA, Fortunato, FL Jr & Pinsky, MR (1993) Postreperfusion syndrome: hypotension after reperfusion of the transplanted liver. Journal of Critical Care 8, 154160.CrossRefGoogle ScholarPubMed
Albina, JE, Mills, CD, Barbul, A, Thirkill, CE, Henry, WL Jr, Mastrofrancesco, B & Caldwell, MD (1988) Arginine metabolism in wounds. American Journal of Physiology 254, E459E467.Google ScholarPubMed
Albina, JE, Mills, CD, Henry, WL Jr & Caldwell, MD (1990) Temporal expression of different pathways of L -arginine metabolism in healing wounds. Journal of Immunology 144, 38773880.CrossRefGoogle ScholarPubMed
Angele, MK, Nitsch, SM, Hatz, RA, Angele, P, Hernandez-Richter, T, Wichmann, MW, Chaudry, IH & Schildberg, FW (2002) L -Arginine: a unique amino acid for improving depressed wound immune function following hemorrhage. European Surgical Research 34, 5360.CrossRefGoogle ScholarPubMed
Angus, DC, Linde-Zwirble, WT, Lidicker, J, Clermont, G, Carcillo, J, & Pinsky, MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Critical Care Medicine 29, 13031310.CrossRefGoogle ScholarPubMed
Annane, D, Sanquer, S, Sebille, V, Faye, A, Djuranovic, D, Raphael, JC, Gajdos, P & Bellissant, E (2000) Compartmentalised inducible nitric-oxide synthase activity in septic shock. Lancet 355, 11431148.CrossRefGoogle ScholarPubMed
Arbss, MA, Ferrando, JM, Vidal, J, Quiles, MT, Huguet, P, Castells, J, Segarra, A, Armengol, M & Schwartz, S (2000) Early effects of exogenous arginine after the implantation of prosthetic material into the rat abdominal wall. Life Sciences 67, 24932512.CrossRefGoogle ScholarPubMed
Argaman, Z, Young, VR, Noviski, N, Castillo-Rosas, L, Lu, XM, Zurakowski, D, Cooper, M, Davison, C, Tharakan, JF, Ajami, A & Castillo, L (2003) Arginine and nitric oxide metabolism in critically ill septic pediatric patients. Critical Care Medicine 31, 591597.CrossRefGoogle ScholarPubMed
Arnal, JF, Dinh-Xuan, AT, Pueyo, M, Darblade, B, & Rami, J (1999) Endothelium-derived nitric oxide and vascular physiology and pathology. Cellular and Molecular Life Sciences 55, 10781087.CrossRefGoogle ScholarPubMed
Baltaci, S, Orhan, D, Gogus, C, Turkolmez, K, Tulunay, O & Gogus, O (2001) Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low- and high-grade prostatic intraepithelial neoplasia and prostatic carcinoma. BJU International 88, 100103.CrossRefGoogle ScholarPubMed
Bankir, L (1996) Urea and the Kidney. Philadelphia, PA: W.B. Saunders Company.Google Scholar
Barbul, A (1990) Arginine and immune function. Nutrition 6, 53–58, discussion 5962.Google ScholarPubMed
Barbul, A, Lazarou, SA, Efron, DT, Wasserkrug, HL & Efron, G (1990) Arginine enhances wound healing and lymphocyte immune responses in humans. Surgery 108, 331–336, discussion 336337.Google ScholarPubMed
Beach, PK, Spain, DA, Kawabe, T, Harris, PD & Garrison, RN (2001) Sepsis increases NOS-2 activity and decreases non-NOS-mediated acetylcholine-induced dilation in rat aorta. Journal of Surgical Research 96, 1722.CrossRefGoogle ScholarPubMed
Bode-Boger, SM, Boger, RH, Galland, A, Tsikas, D & Frolich, JC (1998) L -Arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. British Journal of Clinical Pharmacology 46, 489497.CrossRefGoogle ScholarPubMed
Boger, RH & Bode-Boger, SM (2001) The clinical pharmacology of L -arginine. Annual Review of Pharmacology and Toxicology 41, 7999.CrossRefGoogle ScholarPubMed
Boros, P, Tarcsafalvi, A, Wang, L, Megyesi, J, Liu, J & Miller, CM (2001) Intrahepatic expression and release of vascular endothelial growth factor following orthotopic liver transplantation in the rat. Transplantation 72, 805811.CrossRefGoogle ScholarPubMed
Braillon, A, Cales, P, Valla, D, Gaudy, D, Geoffroy, P & Lebrec, D (1986) Influence of the degree of liver failure on systemic and splanchnic haemodynamics and on response to propranolol in patients with cirrhosis. Gut 27, 12041209.CrossRefGoogle ScholarPubMed
Brealey, D, Brand, M, Hargreaves, I, Heales, S, Land, J, Smolenski, R, Davies, NA, Cooper, CE & Singer, M (2002) Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 360, 219223.CrossRefGoogle ScholarPubMed
Brittenden, J, Heys, SD, Ross, J, Park, KG & Eremin, O (1994 a) Natural cytotoxicity in breast cancer patients receiving neoadjuvant chemotherapy: effects of L -arginine supplementation. European Journal of Surgical Oncology 20, 467472.Google ScholarPubMed
Brittenden, J, Park, KG, Heys, SD, Ross, C, Ashby, J, Ah-See, A & Eremin, O (1994 b) L -Arginine stimulates host defenses in patients with breast cancer. Surgery 115, 205212.Google ScholarPubMed
Bronte, V, Serafini, P, Mazzoni, A, Segal, DM & Zanovello, P (2003) L -Arginine metabolism in myeloid cells controls T-lymphocyte functions. Trends in Immunology 24, 302306.CrossRefGoogle ScholarPubMed
Brosnan, JT (1987) The 1986 Borden Award Lecture. The role of the kidney in amino acid metabolism and nutrition. Canadian Journal of Physiology and Pharmacology 65, 23552362.CrossRefGoogle ScholarPubMed
Bruins, MJ, Lamers, WH, Meijer, AJ, Soeters, PB & Deutz, NE (2002 a) In vivo measurement of nitric oxide production in porcine gut, liver and muscle during hyperdynamic endotoxaemia. British Journal of Pharmacology 137, 12251236.CrossRefGoogle ScholarPubMed
Bruins, MJ, Soeters, PB, Lamers, WH & Deutz, NE (2002 b) L -Arginine supplementation in pigs decreases liver protein turnover and increases hindquarter protein turnover both during and after endotoxemia. American Journal of Clinical Nutrition 75, 10311044.CrossRefGoogle ScholarPubMed
Bruins, MJ, Soeters, PB, Lamers, WH, Meijer, AJ, & Deutz, NEP (2002 c) L -Arginine supplementation in hyperdynamic endotoxemic pigs: effect on nitric oxide synthesis by the different organs. Critical Care Medicine 30, 508517.CrossRefGoogle ScholarPubMed
Bune, AJ, Shergill, JK, Cammack, R & Cook, HT (1995) L -Arginine depletion by arginase reduces nitric oxide production in endotoxic shock: an electron paramagnetic resonance study. FEBS Letters 366, 127130.CrossRefGoogle ScholarPubMed
Burra, P, Chirizzi, L, Cardin, R, Cadrobbi, R, Baldan, N, Calabrese, F, Pettenazzo, E, Calo, L, Plebani, M & Rigotti, P (2001) Warm hepatic ischemia in pigs: effects of L -arginine and oligotide treatment. Journal of Investigative Surgery 14, 303312.CrossRefGoogle ScholarPubMed
Bzeizi, KI, Jalan, R, Henderson, N, Thomas, HW, Lee, A & Hayes, PC (1997) Influence of cyclic guanosine monophosphate changes on hemodynamics after reperfusion in liver transplantation. Transplantation 63, 403406.CrossRefGoogle ScholarPubMed
Calkins, CM, Bensard, DD, Heimbach, JK, Meng, X, Shames, BD, Pulido, EJ & McIntyre, RC Jr (2001) L -Arginine attenuates lipopolysaccharide-induced lung chemokine production. American Journal of Physiology 280, L400–L408Google ScholarPubMed
Canturk, NZ, Vural, B, Canturk, Z, Esen, N, Vural, S, Solakoglu, S & Kirkal, G (2001) The role of L -arginine and neutrophils on incisional wound healing. European Journal of Emergency Medicine 8, 311315.CrossRefGoogle ScholarPubMed
Castillo, L, Beaumier, L, Ajami, AM & Young, VR (1996) Whole body nitric oxide synthesis in healthy men determined from [ 15N] arginine-to-[ 15N]citrulline labeling. Proceedings of the National Academy of Sciences USA 93, 1146011465.CrossRefGoogle ScholarPubMed
Castillo, L, Sanchez, M, Vogt, J, Chapman, TE, DeRojas-Walker, TC, Tannenbaum, SR, Ajami, AM & Young, VR (1995) Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis. American Journal of Physiology 268, E360–E367.Google ScholarPubMed
Chamuleau, RAFM, Deutz, NEP, de Haan, JG & van Gool, J (1987) Correlation between electroencephalographic and biochemical indices in acute hepatic encephalopathy in rats. Journal of Hepatology 4, 299306.CrossRefGoogle ScholarPubMed
Chen, K, Inoue, M, Wasa, M, Fukuzawa, M, Kamata, S & Okada, A (1997) Expression of endothelial constitutive nitric oxide synthase mRNA in gastrointestinal mucosa and its downregulation by endotoxin. Life Sciences 61, 13231329.CrossRefGoogle ScholarPubMed
Choe, W, Kim, S, Hwang, TS & Lee, SS (2003) Expression of inducible nitric oxide synthase in thyroid neoplasms: immunohistochemical and molecular analysis. Pathology International 53, 434439.CrossRefGoogle ScholarPubMed
Cianchi, F, Cortesini, C, Fantappie, O, Messerini, L, Schiavone, N, Vannacci, A, Nistri, S, Sardi, I, Baroni, G, Marzocca, C, Perna, F, Mazzanti, R, Bechi, P & Masini, E (2003) Inducible nitric oxide synthase expression in human colorectal cancer: correlation with tumor angiogenesis. American Journal of Pathology 162, 793801.CrossRefGoogle ScholarPubMed
Clavien, PA, Camargo, CA Jr, Gorczynski, R, Washington, MK, Levy, GA, Langer, B, & Greig, PD (1996) Acute reactant cytokines and neutrophil adhesion after warm ischemia in cirrhotic and noncirrhotic human livers. Hepatology 23, 14561463.CrossRefGoogle ScholarPubMed
Cobbs, CS, Brenman, JE, Aldape, KD, Bredt, DS & Israel, MA (1995) Expression of nitric oxide synthase in human central nervous system tumors. Cancer Research 55, 727730.Google ScholarPubMed
Colletti, LM, Kunkel, SL, Walz, A, Burdick, MD, Kunkel, RG, Wilke, CA & Strieter, RM (1995) Chemokine expression during hepatic ischemia/reperfusion-induced lung injury in the rat. The role of epithelial neutrophil activating protein. Journal of Clinical Investigations 95, 134141.CrossRefGoogle ScholarPubMed
Crenn, P, Coudray-Lucas, C, Cynober, L & Messing, B (1998) Postabsorptive plasma citrulline concentration: a marker of intestinal failure in humans. Transplantation Proceedings 30, 2528.CrossRefGoogle ScholarPubMed
Crenn, P, Coudray-Lucas, C, Thuillier, F, Cynober, L & Messing, B (2000) Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology 119, 14961505.CrossRefGoogle ScholarPubMed
Crenn, P, Vahedi, K, Lavergne-Slove, A, Cynober, L, Matuchansky, C & Messing, B (2003) Plasma citrulline: a marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology 124, 12101219.CrossRefGoogle ScholarPubMed
Cynober, L (1994) Can arginine and ornithine support gut functions? Gut 35, Suppl. 1, S42S45.CrossRefGoogle ScholarPubMed
Cynober, L, Le Boucher, J & Vasson, M-P (1995) Arginine metabolism in mammals. Journal of Nutritional Biochemistry 6, 402403.CrossRefGoogle Scholar
Daly, JM, Reynolds, J, Thom, A, Kinsley, L, Dietrick-Gallagher, M, Shou, J & Ruggieri, B (1988) Immune and metabolic effects of arginine in the surgical patient. Annals of Surgery 208, 512523.CrossRefGoogle ScholarPubMed
De Backer, D, Creteur, JPreiser, JC, Dubois, MJ & Vincent, JL (2002) Microvascular blood flow is altered in patients with sepsis. American Journal of Respiratory and Critical Care Medicine 166, 98104.CrossRefGoogle ScholarPubMed
Dedio, J, Konig, P, Wohlfart, P, Schroeder, C, Kummer, W & Muller-Esterl, W (2001) NOSIP, a novel modulator of endothelial nitric oxide synthase activity. FASEB Journal 15, 7989.CrossRefGoogle ScholarPubMed
Dejong, CHC, Deutz, NEP & Soeters, PB (1993 a) Intestinal glutamine and ammonia metabolism during chronic hyperammonaemia induced by liver insufficiency. Gut 34, 11121119.CrossRefGoogle ScholarPubMed
Dejong, CHC, Deutz, NEP & Soeters, PB (1993 b) Metabolic adaptation of the kidney to hyperammonemia during chronic liver insufficiency in the rat. Hepatology 18, 890902.CrossRefGoogle ScholarPubMed
Dejong, CHC, Welters, CFM, Deutz, NEP, Heineman, E & Soeters, PB (1998) Renal arginine metabolism in fasted rats with subacute short bowel syndrome. Clinical Science 95, 409418.CrossRefGoogle ScholarPubMed
de Knegt, RJ, Schalm, SW, van der Rijt, CC, Fekkes, D, Dalm, E & Hekking-Weyma, I (1994) Extracellular brain glutamate during acute liver failure and during acute hyperammonemia simulating acute liver failure: an experimental study based on in vivo brain dialysis. Journal of Hepatology 20, 1926.CrossRefGoogle ScholarPubMed
Deutz, NEP, Bruins, MJ & Soeters, PB (1998) Infusion of soy and casein protein meals affects interorgan amino acid metabolism and urea kinetics differently in pigs. Journal of Nutrition 128, 24352445.CrossRefGoogle ScholarPubMed
Deutz, NEP, Dejong, CHC, Athanasas, G & Soeters, PB (1992) Partial enterectomy in the rat does not diminish muscle glutamine production. Metabolism 41, 13431350.CrossRefGoogle Scholar
de Werra, I, Jaccard, C, Corradin, SB, Chiolero, R, Yersin, B, Gallati, H, Assicot, M, Bohuon, C, Baumgartner, JD, Glauser, MP & Heumann, D (1997) Cytokines, nitrite/nitrate, soluble tumor necrosis factor receptors, and procalcitonin concentrations: comparisons in patients with septic shock, cardiogenic shock, and bacterial pneumonia. Critical Care Medicine 25, 607613.CrossRefGoogle ScholarPubMed
Dhanakoti, SN, Brosnan, JT, Herzberg, GR & Brosnan, ME (1990) Renal arginine synthesis: studies in vitro and in vivo. American Journal of Physiology 259, E437E442.Google ScholarPubMed
Dickinson, E, Tuncer, R, Nadler, E, Boyle, P, Alber, S, Watkins, S & Ford, H (1999) NOx, a novel nitric oxide scavenger, reduces bacterial translocation in rats after endotoxin challenge. American Journal of Physiology 277, G1281G1287.Google ScholarPubMed
Diwan, AD, Wang, MX, Jang, D, Zhu, W & Murrell, GA (2000) Nitric oxide modulates fracture healing. Journal of Bone and Mineral Research 15, 342351.CrossRefGoogle ScholarPubMed
Edwards, PD, Topping, D, Kontaridis, MI, Moldawer, LL, Copeland EM, 3 & Lind, DS (1997) Arginine-enhanced enteral nutrition augments the growth of a nitric oxide-producing tumor. Journal of Parenteral and Enteral Nutrition 21, 215219.CrossRefGoogle ScholarPubMed
Efron, D & Barbul, A (2000) Role of arginine in immunonutrition. Journal of Gastroenterology 35, Suppl. 12, 2023.Google ScholarPubMed
Endo, S, Inada, K, Nakae, H, Arakawa, N, Takakuwa, T, Yamada, Y, Shimamura, T, Suzuki, T, Taniguchi, S & Yoshida, M (1996) Nitrite/nitrate oxide (NOx) and cytokine levels in patients with septic shock. Research Communications in Molecular Pathology and Pharmacology 91, 347356.Google ScholarPubMed
Evans, T, Carpenter, A, Kinderman, H & Cohen, J (1993) Evidence of increased nitric oxide production in patients with the sepsis syndrome. Circulatory Shock 41, 7781.Google ScholarPubMed
Flynn, NE, Meininger, CJ, Haynes, TE & Wu, G (2002) The metabolic basis of arginine nutrition and pharmacotherapy. Biomedicine and Pharmacotherapy 56, 427438.CrossRefGoogle ScholarPubMed
Freund, H, Atamian, S, Holroyde, J & Fischer, JE (1979) Plasma amino acids as predictors of the severity and outcome of sepsis. Annals of Surgery 190, 571576.CrossRefGoogle ScholarPubMed
Gallo, O, Schiavone, N, Papucci, L, Sardi, I, Magnelli, L, Franchi, A, Masini, E & Capaccioli, S (2003) Down-regulation of nitric oxide synthase-2 and cyclooxygenase-2 pathways by P53 in squamous cell carcinoma. American Journal of Pathology 163, 723732.CrossRefGoogle ScholarPubMed
Garcia-Martinez, C, Llovera, M, Lopez-Soriano, FJ & Argiles, JM (1993) The effects of endotoxin administration on blood amino acid concentrations: similarities with sepsis. Cellular and Molecular Biology 39, 537542.Google ScholarPubMed
Gerlach, J, Jorres, A, Schon, M, Nohr, R, Berger, A, Spatkowski, G, Smith, MD & Neuhaus, P (1997) Systemic liberation of interleukin-8 in the perioperative phase of liver transplantation. Transplant International 10, 401404.CrossRefGoogle ScholarPubMed
Gewaltig, MT & Kojda, G (2002) Vasoprotection by nitric oxide: mechanisms and therapeutic potential. Cardiovascular Research 55, 250260.CrossRefGoogle ScholarPubMed
Gianotti, L, Alexander, JW, Pyles, T & Fukushima, R (1993) Arginine-supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance. The role of nitric oxide. Annals of Surgery 217, 644–653, discussion 653654.CrossRefGoogle ScholarPubMed
Glass, RE, Goode, AW, Houghton, BJ & Rowell, LW (1986) Plasma arginine in cancer of the gastrointestinal tract: effect of surgical treatment. Gut 27, 844848.CrossRefGoogle ScholarPubMed
Gokmen, SS, Aygit, AC, Ayhan, MS, Yorulmaz, F & Gulen, S (2001) Significance of arginase and ornithine in malignant tumors of the human skin. Journal of Laboratory and Clinical Medicine 137, 340344.CrossRefGoogle ScholarPubMed
Gomez-Jimenez, J, Salgado, A, Mourelle, M, Martin, MC, Segura, RM, Peracaula, R, & Moncada, S (1995) L -Arginine: nitric oxide pathway in endotoxemia and human septic shock. Critical Care Medicine 23, 253258.CrossRefGoogle ScholarPubMed
Gonce, SJ, Peck, MD, Alexander, JW, Miskell, PW (1990) Arginine supplementation and its effect on established peritonitis in guinea pigs. Journal of Parenteral and Enteral Nutrition 14, 237244.CrossRefGoogle ScholarPubMed
Goode, HF, Webster, NR, Howdle, PD, Leek, JP, Lodge, JP, Sadek, SA & Walker, BE (1994) Reperfusion injury, antioxidants and hemodynamics during orthotopic liver transplantation. Hepatology 19, 354359.CrossRefGoogle ScholarPubMed
Groeneveld, AB, Hartemink, KJ, de Groot, MC, Visser, J & Thijs, LG (1999) Circulating endothelin and nitrate-nitrite relate to hemodynamic and metabolic variables in human septic shock. Shock 11, 160166.CrossRefGoogle ScholarPubMed
Groeneveld, PH, Kwappenberg, KM, Langermans, JA, Nibbering, PH & Curtis, L (1996) Nitric oxide (NO) production correlates with renal insufficiency and multiple organ dysfunction syndrome in severe sepsis. Intensive Care Medicine 22, 11971202.CrossRefGoogle ScholarPubMed
Groeneveld, PH, Kwappenberg, KM, Langermans, JA, Nibbering, PH & Curtis, L (1997) Relation between pro- and anti-inflammatory cytokines and the production of nitric oxide (NO) in severe sepsis. Cytokine 9, 138142.CrossRefGoogle ScholarPubMed
Groszmann, RJ (1993) Hyperdynamic state in chronic liver diseases. Journal of Hepatology 17, Suppl. 2, S38S40.CrossRefGoogle ScholarPubMed
Guarner, C, Soriano, G, Tomas, A, Bulbena, O, Novella, MT, Balanzo, J, Vilardell, F, Mourelle, M & Moncada, S (1993) Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia. Hepatology 18, 11391143.CrossRefGoogle ScholarPubMed
Hallemeesch, MM, Cobben, DC, Soeters, PB & Deutz, NE (2002 a) Differential effects of selective and non-selective NOS inhibition on renal arginine and protein metabolism during endotoxemia in rats. Clinical Nutrition 21, 111117.CrossRefGoogle ScholarPubMed
Hallemeesch, MM, Janssen, BJ, De Jonge, WJ, Soeters, PB, Lamers, WH & Deutz, NE (2003) Increased iNOS-mediated and decreased cNOS-mediated NO production reflect blood pressure changes in LPS-challenged mice. American Journal of Physiology 285, E871E875.Google Scholar
Hallemeesch, MM, Lamers, WH & Deutz, NE (2002 b) Reduced arginine availability and nitric oxide production. Clinical Nutrition 21, 273279.CrossRefGoogle ScholarPubMed
Hallemeesch, MM, Soeters, PB & Deutz, NE (2002 c) Renal arginine and protein synthesis are increased during early endotoxemia in mice. American Journal of Physiology 282, F316F323.Google ScholarPubMed
Hammarqvist, F, Wernerman, J, Ali, R, von der Decken, A & Vinnars, E (1989) Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves n balance. Annals of Surgery 209, 455461.CrossRefGoogle Scholar
Harrison, DG & Cai, H (2003) Endothelial control of vasomotion and nitric oxide production. Cardiology Clinics 21, 289302.CrossRefGoogle ScholarPubMed
Hazell, AS & Norenberg, MD (1998) Ammonia and manganese increase arginine uptake in cultured astrocytes. Neurochemical Research 23, 869873.CrossRefGoogle ScholarPubMed
Helmer, KS, West, SD, Shipley, GL, Chang, L, Cui, Y, Mailman, D & Mercer, DW (2002) Gastric nitric oxide synthase expression during endotoxemia: implications in mucosal defense in rats. Gastroenterology 123, 173186.CrossRefGoogle ScholarPubMed
Helmy, A, Newby, DE, Jalan, R, Johnston, NR, Hayes, PC & Webb, DJ (2003) Nitric oxide mediates the reduced vasoconstrictor response to angiotensin ii in patients with preascitic cirrhosis. Journal of Hepatology 38, 4450.CrossRefGoogle ScholarPubMed
Heyland, DK, Novak, F, Drover, JW, Jain, M, Su, X & Suchner, U (2001) Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. Journal of the American Medical Association 286, 944953.CrossRefGoogle ScholarPubMed
Heyland, DK & Samis, A (2003) Does immunonutrition in patients with sepsis do more harm than good? Intensive Care Medicine 29, 669671.CrossRefGoogle ScholarPubMed
Heys, SD & Ashkanani, F (1999) Glutamine. British Journal of Surgery 86, 289290.CrossRefGoogle ScholarPubMed
Heys, SD & Gardner, E (1999) Nutrients and the surgical patient: current and potential therapeutic applications to clinical practice. Journal of the Royal College of Surgeons of Edinburgh 44, 283293.Google ScholarPubMed
Heys, SD, Segar, A, Payne, S, Bruce, DM, Kernohan, N & Eremin, O (1997) Dietary supplementation with L -arginine: modulation of tumour-infiltrating lymphocytes in patients with colorectal cancer. British Journal of Surgery 84, 238241.Google Scholar
Hibbs, JB Jr, Vavrin, Z & Taintor, RR (1987) L -Arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. Journal of Immunology 138, 550565.CrossRefGoogle ScholarPubMed
Hiltebrand, LB, Krejci, V, Banic, A, Erni, D, Wheatley, AM & Sigurdsson, GH (2000) Dynamic study of the distribution of microcirculatory blood flow in multiple splanchnic organs in septic shock. Critical Care Medicine 28, 32333241.CrossRefGoogle ScholarPubMed
Hoffman, RA, Zhang, G, Nussler, NC, Gleixner, SL, Ford, HR, Simmons, RL & Watkins, SC (1997) Constitutive expression of inducible nitric oxide synthase in the mouse ileal mucosa. American Journal of Physiology 272, G383G392.Google ScholarPubMed
Hoogenraad, N, Totino, N, Elmer, H, Wraight, C, Alewood, P & Johns, B (1985) Inhibition of intestinal citrulline synthesis causes severe growth retardation in rats. American Journal of Physiology 249, G792G799.Google ScholarPubMed
Houdijk, APJ, Rijnsburger, ER, Jansen, J, Wesdorp, RIC, Weiss, JK, McCamish, MA, Teerlink, T, Meuwissen, SGM, Haarman, HJTM, Thijs, LG & van Leeuwen, PAM (1998 a) Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 352, 772776.CrossRefGoogle ScholarPubMed
Houdijk, APJ, van Leeuwen, PAM, Teerlink, T, Flinkerbusch, EL, Boermeester, MA, Sauerwein, HP & Wesdorp, RIC (1994) Glutamine-enriched enteral diet increases renal arginine production. Journal of Parenteral and Enteral Nutrition 18, 422426.CrossRefGoogle ScholarPubMed
Houdijk, APJ, Visser, JJ, Rijnsburger, ER, Teerlink, T, van Leeuwen, PAM (1998 b) Dietary glutamine supplementation reduces plasma nitrate levels in rats. Clinical Nutrition 17, 1114.CrossRefGoogle ScholarPubMed
Ikemoto, M, Tsunekawa, S, Tanaka, K, Tanaka, A, Yamaoka, Y, Ozawa, K, Fukuda, Y, Moriyasu, F, Totani, M, Kasai, Y, Mori, T & Ueda, K (1998) Liver-type arginase in serum during and after liver transplantation: a novel index in monitoring conditions of the liver graft and its clinical significance. Clinica Chimica Acta 271, 1123.CrossRefGoogle ScholarPubMed
Ito, A, Tsao, PS, Adimoolam, S, Kimoto, M, Ogawa, T & Cooke, JP (1999) Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 99, 30923095.CrossRefGoogle ScholarPubMed
Jacobs, DO, Evans, DA, Mealy, K, O'Dwyer, ST, Smith, RJ & Wilmore, DW (1988) Combined effects of glutamine and epidermal growth factor on the rat intestine. Surgery 104, 358364.Google ScholarPubMed
Jalkanen, M, Larjava, H, Heino, J, Vihersaari, T, Peltonen, J & Penttinen, R (1982) Arginine depletion in macrophage medium inhibits collagen synthesis by fibroblasts. Immunology Letters 4, 259261.CrossRefGoogle ScholarPubMed
Jayasurya, A, Dheen, ST, Yap, WM, Tan, NG, Ng, YK & Bay, BH (2003) Inducible nitric oxide synthase and bcl-2 expression in nasopharyngeal cancer: correlation with outcome of patients after radiotherapy. International Journal of Radiation Oncology, Biology, Physics 56, 837845.CrossRefGoogle ScholarPubMed
John, S & Schmieder, RE (2003) Potential mechanisms of impaired endothelial function in arterial hypertension and hypercholesterolemia. Current Hypertension Reports 5, 199207.CrossRefGoogle ScholarPubMed
Ju, H, Zou, R, Venema, VJ & Venema, RC (1997) Direct interaction of endothelial nitric-oxide synthase and caveolin-1 inhibits synthase activity. Journal of Biological Chemistry 272, 1852218525.CrossRefGoogle ScholarPubMed
Kampfer, H, Pfeilschifter, J & Frank, S (2003) Expression and activity of arginase isoenzymes during normal and diabetes-impaired skin repair. Journal of Investigative Dermatology 121, 15441551.CrossRefGoogle ScholarPubMed
Katchman, AN & Hershkowitz, N (1997) Nitric oxide modulates synaptic glutamate release during anoxia. Neuroscience Letters 228, 5054.CrossRefGoogle ScholarPubMed
Kato, S, Esumi, H, Hirano, A, Kato, M, Asayama, K & Ohama, E (2003) Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in human brain tumors: relationships of iNOS to superoxide dismutase (SOD) proteins (SOD1 and SOD2), Ki-67 antigen (Mib-1) and P53 protein. Acta Neuropathologica 105, 333340.CrossRefGoogle ScholarPubMed
Kelly, E, Morris, SM Jr & Billiar, TR (1995) Nitric oxide, sepsis, and arginine metabolism. Journal of Parenteral and Enteral Nutrition 19, 234238.CrossRefGoogle ScholarPubMed
Keskinege, A, Elgun, S & Yilmaz, E (2001) Possible implications of arginase and diamine oxidase in prostatic carcinoma. Cancer Detection and Prevention 25, 7679.Google ScholarPubMed
Kielstein, JT, Bode-Boger, SM, Frolich, JC, Ritz, E, Haller, H & Fliser, D (2003) Asymmetric dimethylarginine, blood pressure, and renal perfusion in elderly subjects. Circulation 107, 18911895.CrossRefGoogle ScholarPubMed
Kilbourn, R (1999) Nitric oxide synthase inhibitors – a mechanism-based treatment of septic shock. Critical Care Medicine 27, 857858.CrossRefGoogle ScholarPubMed
Kirk, SJ & Barbul, A (1990) Role of arginine in trauma, sepsis, and immunity. Journal of Parenteral and Enteral Nutrition 14, 226S229S.CrossRefGoogle ScholarPubMed
Kirk, SJ, Hurson, M, Regan, MC, Holt, DR, Wasserkrug, HL & Barbul, A (1993) Arginine stimulates wound healing and immune function in elderly human beings. Surgery 114, 155–159, discussion 160.Google ScholarPubMed
Kirkeboen, KA & Strand, OA (1999) The role of nitric oxide in sepsis – an overview. Acta Anaesthesiologica 43, 275288.CrossRefGoogle ScholarPubMed
Klimberg, VS, Salloum, RM, Kasper, M, Plumley, DA, Dolson, DJ, Hautamaki, RD, Mendenhall, WR, Bova, FC, Bland, KI, Copeland, EM & Souba, WW (1990 a) Oral glutamine accelerates healing of the small intestine and improves outcome after whole abdominal radiation. Archives of Surgery 125, 10401045.CrossRefGoogle ScholarPubMed
Klimberg, VS, Souba, WW, Salloum, RM, Holley, DT, Hautamaki, RD, Dolson, DJ & Copeland, EM (1990 b) Intestinal glutamine metabolism after massive small bowel resection. American Journal of Surgery 159, 2733.CrossRefGoogle ScholarPubMed
Kong, G, Kim, EK, Kim, WS, Lee, KT, Lee, YW, Lee, JK, Paik, SW & Rhee, JC (2002) Role of cyclooxygenase-2 and inducible nitric oxide synthase in pancreatic cancer. Journal of Gastroenterology and Hepatology 17, 914921.CrossRefGoogle ScholarPubMed
Konig, P, Dedio, J, Muller-Esterl, W & Kummer, W (2002) Distribution of the novel eNOS-interacting protein NOSIP in the liver, pancreas, and gastrointestinal tract of the rat. Gastroenterology 123, 314324.Google ScholarPubMed
Kubota, A, Meguid, MM & Hitch, DC (1992) Amino acid profiles correlate diagnostically with organ site in three kinds of malignant tumors. Cancer 69, 23432348.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
Lancaster, JR Jr & Hibbs, JB Jr (1990) EPR demonstration of Fe-nitrosyl complex formation by cytotoxic activated macrophages. Proceedings of the National Acadamy of Sciences USA 87, 12231227.CrossRefGoogle Scholar
Langle, F, Roth, E, Steininger, R, Winkler, S & Muhlbacher, F (1995) Arginase release following liver reperfusion. Evidence of hemodynamic action of arginase infusions. Transplantation 59, 15421549.CrossRefGoogle ScholarPubMed
Langle, F, Steininger, R, Waldmann, E, Grunberger, T, Benditte, H, Mittlbock, M, Soliman, T, Schindl, M, Windberger, U, Muhlbacher, F & Roth, E (1997) Improvement of cardiac output and liver blood flow and reduction of pulmonary vascular resistance by intravenous infusion of L -arginine during the early reperfusion period in pig liver transplantation. Transplantation 63, 12251233.CrossRefGoogle ScholarPubMed
Lavoie, J, Giguere, JF, Layrargues, GP & Butterworth, RF (1987) Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. Journal of Neurochemistry 49, 692697.CrossRefGoogle ScholarPubMed
Lee, PC, Salyapongse, AN, Bragdon, GA, Shears LL, 2, Watkins, SC, Edington, HD & Billiar, TR (1999) Impaired wound healing and angiogenesis in eNOS-deficient mice. American Journal of Physiology 277, H1600H1608.Google ScholarPubMed
Lee, RH, Efron, D, Tantry, U & Barbul, A (2001) Nitric oxide in the healing wound: a time-course study. Journal of Surgical Research 101, 104108.CrossRefGoogle ScholarPubMed
Lee, TW, Chen, GG, Xu, H, Yip, JH, Chak, EC, Mok, TS & Yim, AP (2003) Differential expression of inducible nitric oxide synthase and peroxisome proliferator-activated receptor gamma in non-small cell lung carcinoma. European Journal of Cancer 39, 12961301.CrossRefGoogle ScholarPubMed
Lentsch, AB, Yoshidome, H, Cheadle, WG, Miller, FN & Edwards, MJ (1998) Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and Kc. Hepatology 27, 11721177.CrossRefGoogle ScholarPubMed
Lieberman, MD, Nishioka, K, Redmond, HP & Daly, JM (1992) Enhancement of interleukin-2 immunotherapy with L -arginine. Annals of Surgery 215, 157165.CrossRefGoogle ScholarPubMed
Lin, KY, Ito, A, Asagami, T, Tsao, PS, Adimoolam, S, Kimoto, M, Tsuji, H, Reaven, GM, Cooke, JP & (2002) Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 106, 987992.CrossRefGoogle ScholarPubMed
Liu, Q, Chan, ST & Mahendran, R (2003) Nitric oxide induces cyclooxygenase expression and inhibits cell growth in colon cancer cell lines. Carcinogenesis 24, 637642.CrossRefGoogle ScholarPubMed
Lorente, JA, Delgado, MA, Tejedor, C, Mon, E, Hervas, M, Pascual, T, Fernandez-Segoviano, P, Rieppi, G, Soler, A, Ayuso, D & Esteban, A (1999) Modulation of systemic hemodynamics by exogenous L -arginine in normal and bacteremic sheep. Critical Care Medicine 27, 24742479.CrossRefGoogle ScholarPubMed
Lorente, JA, Landin, L, De Pablo, R, Renes, E, Liste, D (1993 a) L -Arginine pathway in the sepsis syndrome. Critical Care Medicine 21, 12871295.CrossRefGoogle ScholarPubMed
Lorente, JA, Landin, L, Renes, E, De Pablo, R, Jorge, P, Rodena, E & Liste, D (1993 b) Role of nitric oxide in the hemodynamic changes of sepsis. Critical Care Medicine 21, 759767.CrossRefGoogle ScholarPubMed
Lubec, B, Hoeger, H, Kremser, K, Amann, G, Koller, DY & Gialamas, J (1996) Decreased tumor incidence and increased survival by one year oral low dose arginine supplementation in the mouse. Life Sciences 58, 23172325.CrossRefGoogle ScholarPubMed
Luiking, YC & Deutz, NE (2003) Isotopic investigation of nitric oxide metabolism in disease. Current Opinion in Clinical Nutrition and Metabolic Care 6, 103108.CrossRefGoogle ScholarPubMed
MacAllister, RJ, Parry, H, Kimoto, M, Ogawa, T, Russell, RJ, Hodson, H, Whitley, GS & Vallance, P (1996) Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. British Journal of Pharmacology 119, 15331540.CrossRefGoogle ScholarPubMed
McCarter, MD, Gentilini, OD, Gomez, ME & Daly, JM (1998) Preoperative oral supplement with immunonutrients in cancer patients. Journal of Parenteral and Enteral Nutrition 22, 206211.CrossRefGoogle ScholarPubMed
MacKenzie, IM, Garrard, CS & Young, JD (2001) Indices of nitric oxide synthesis and outcome in critically ill patients. Anaesthesia 56, 326330.CrossRefGoogle ScholarPubMed
Manders, S, Poeze, M, Ramsay, G, Greve, JWM & Deutz, NEP (1999) Plasma nitrate in surviving patients with septic shock are increased compared with non-survivors. Intensive Care Medicine 25, S86.Google Scholar
Mendes, RV, Martins, AR, de Nucci, G, Murad, F & Soares, FA (2001) Expression of nitric oxide synthase isoforms and nitrotyrosine immunoreactivity by B-cell non-Hodgkin's lymphomas and multiple myeloma. Histopathology 39, 172178.CrossRefGoogle ScholarPubMed
Milewski, PJ, Threlfall, CJ, Heath, DF, Holbrook, IB, Wilford, K & Irving, MH (1982) Intracellular free amino acids in undernourished patients with or without sepsis. Clinical Science (London) 62, 8391.CrossRefGoogle ScholarPubMed
Miller, MJ, Thompson, JH & Zhang, XJ, et al. (1995) Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis. Gastroenterology 109, 14751483.CrossRefGoogle ScholarPubMed
Millis, RM, Diya, CA, Reynolds, ME, Dehkordi, O & Bond, V Jr (1998) Growth inhibition of subcutaneously transplanted hepatomas without cachexia by alteration of the dietary arginine-methionine balance. Nutrition and Cancer 31, 4955.CrossRefGoogle ScholarPubMed
Milner, JA & Stepanovich, LV (1979) Inhibitory effect of dietary arginine on growth of Ehrlich ascites tumor cells in mice. Journal of Nutrition 109, 489494.CrossRefGoogle ScholarPubMed
Mishima, S, Xu, D, Lu, Q & Deitch, EA (1998) The relationships among nitric oxide production, bacterial translocation, and intestinal injury after endotoxin challenge in vivo. Journal of Trauma 44, 175182.CrossRefGoogle ScholarPubMed
Moffat, FL Jr, Han, T, Li, ZM, Peck, MD, Jy, W, Ahn, YS, Chu, AJ & Bourguignon, LY (1996) Supplemental L -arginine HCl augments bacterial phagocytosis in human polymorphonuclear leukocytes. Journal of Cellular Physiology 168, 2633.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Morel, F, Hus-Citharel, A & Levillain, O (1996) Biochemical heterogeneity of arginine metabolism along the kidney proximal tubules. Kidney International 49, 16081610.CrossRefGoogle ScholarPubMed
Morris, SM Jr & Billiar, TR (1994) New insights into the regulation of inducible nitric oxide synthesis. American Journal of Physiology 266, E829E839.Google ScholarPubMed
Mungrue, IN, Bredt, DS, Stewart, DJ & Husain, M (2003) From molecules to mammals: what's NOS got to do with it? Acta Physiologica Scandinavica 179, 123135.CrossRefGoogle Scholar
Murohara, T, Asahara, T, Silver, M, Bauters, C, Masuda, H, Kalka, C, Kearney, M, Chen, D, Symes, JF, Fishman, MC, Huang, PL & Isner, JM (1998) Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. Journal of Clinical Investigations 101, 25672578.CrossRefGoogle ScholarPubMed
Murrell, GA, Szabo, C, Hannafin, JA, Jang, D, Dolan, MM, Deng, XH, Murrell, DF & Warren, RF (1997) Modulation of tendon healing by nitric oxide. Inflammation Research 46, 1927.CrossRefGoogle ScholarPubMed
Naini, AB, Dickerson, JW & Brown, MM (1988) Preoperative and postoperative levels of plasma protein and amino acid in esophageal and lung cancer patients. Cancer 62, 355360.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Nakae, H, Endo, S, Kikuchi, M, Yamada, Y, Shibata, M, Ishikura, H, Tanaka, T, Wakabayashi, G, Kawamura, T, Inada, K & Sato, S (2000) Nitrite/nitrate (NOx) levels and hemodynamics during septic shock. Surgery Today 30, 683688.CrossRefGoogle ScholarPubMed
Napoli, C (2002) Nitric oxide and atherosclerotic lesion progression: an overview. Journal of Cardiac Surgery 17, 355362.CrossRefGoogle ScholarPubMed
Napoli, C & Ignarro, LJ (2001) Nitric oxide and atherosclerosis. Nitric Oxide 5, 8897.CrossRefGoogle ScholarPubMed
Newsholme, EA & Leech, AR (1983) Biochemistry for the Medical Sciences. New York: John Wiley & Sons.Google Scholar
Nijveldt, RJ, Teerlink, T, Siroen, MP, van Lambalgen, AA, Rauwerda, JA & van Leeuwen, PA (2003 a) The liver is an important organ in the metabolism of asymmetrical dimethylarginine (ADMA). Clinical Nutrition 22, 1722.CrossRefGoogle Scholar
Nijveldt, RJ, Teerlink, T, van Der Hoven, B, Siroen, MP, Kuik, DJ, Rauwerda, JA & van Leeuwen, PA (2003 b) Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma adma concentration is an independent risk factor of ICU mortality. Clinical Nurtition 22, 2330.Google ScholarPubMed
Nirgiotis, JG, Hennessey, PJ & Andrassy, RJ (1991) The effects of an arginine-free enteral diet on wound healing and immune function in the postsurgical rat. Journal of Pediatric Surgery 26, 936941.CrossRefGoogle ScholarPubMed
Nixon, DW, Heymsfield, SB, Cohen, AE, Kutner, MH, Ansley, J, Lawson, DH & Rudman, D (1980) Protein-calorie undernutrition in hospitalized cancer patients. American Journal of Medicine 68, 683690.CrossRefGoogle ScholarPubMed
Norris, KA, Schrimpf, JE, Flynn, JL & Morris, SM Jr (1995) Enhancement of macrophage microbicidal activity: supplemental arginine and citrulline augment nitric oxide production in murine peritoneal macrophages and promote intracellular killing of Trypanosoma cruzi. Infection and Immunity 63, 27932796.CrossRefGoogle ScholarPubMed
Novaes, MR, Lima, LA, Ribeiro, JE, Magalhaes, AV, Sousa, MV & Morhy, L (2000) Pharmacological effects of arginine supplementation in rats with Walker 256 solid tumor (in Portuguese). Archivos Latinoamericanos de Nutricon 50, 230236.Google Scholar
Ochoa, JB, Udekwu, AO, Billiar, TR, Curran, RD, Cerra, FB, Simmons, RL & Peitzman, AB (1991) Nitrogen oxide levels in patients after trauma and during sepsis. Annals of Surgery 214, 621626.CrossRefGoogle ScholarPubMed
O'Dwyer, ST, Smith, RJ, Hwang, TL & Wilmore, DW (1989) Maintenance of small bowel mucosa with glutamine-enriched parenteral nutrition. Journal of Parenteral and Enteral Nutrition 13, 579585.CrossRefGoogle ScholarPubMed
Ogawa, T, Kimoto, M & Sasaoka, K (1987) Occurrence of a new enzyme catalyzing the direct conversion of NG, NG-dimethyl- L -arginine to L -citrulline in rats. Biochemical and Biophysical Research Communications 148, 671677.CrossRefGoogle Scholar
Oka, T, Ohwada, K, Nagao, M & Kitazato, K (1993) Effect of arginine-enriched total parenteral nutrition on the host-tumor interaction in cancer-bearing rats. Journal of Parenteral and Enteral Nutrition 17, 375383.CrossRefGoogle ScholarPubMed
Oka, T, Ohwada, K, Nagao, M, Kitazato, K & Kishino, Y (1994) Arginine-enriched solution induces a marked increase in muscle glutamine concentration and enhances muscle protein synthesis in tumor-bearing rats. Journal of Parenteral and Enteral Nutrition 18, 491496.CrossRefGoogle ScholarPubMed
Oudenhoven, IM, Klaasen, HL, Lapre, JA, Weerkamp, AH & Van der Meer, R (1994 a) Nitric oxide-derived urinary nitrate as a marker of intestinal bacterial translocation in rats. Gastroenterology 107, 4753.CrossRefGoogle ScholarPubMed
Oudenhoven, IMJ, Klaasen, HLBM, Lapre, JA, Weerkamp, AH & Van der Meer, R (1994 b) Nitric oxide-derived urinary nitrate as a marker of intestinal bacterial translocation in rats. Gastroenterology 107, 4753.CrossRefGoogle ScholarPubMed
Park, KG, Heys, SD, Blessing, K, Kelly, P, McNurlan, MA, Eremin, O & Garlick, PJ (1992) Stimulation of human breast cancers by dietary L -arginine. Clinical Science (London) 82, 413417.CrossRefGoogle ScholarPubMed
Park, KG, Heys, SD, Harris, CI, Steele, RJ, McNurlan, MA, Eremin, O & Garlick, PJ (1991) Arginine metabolism in benign and malignant disease of breast and colon: evidence for possible inhibition of tumor-infiltrating macrophages. Nutrition 7, 185188.Google ScholarPubMed
Parrillo, JE (1993) Pathogenetic mechanisms of septic shock. New England Journal of Medicine 328, 14711477.Google ScholarPubMed
Patel, A, Fenton, C, Terrell, R, Powers, PA, Dinauer, C, Tuttle, RM & Francis, GL (2002) Nitrotyrosine, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) are increased in thyroid tumors from children and adolescents. Journal of Endocrinological Investigation 25, 675683.CrossRefGoogle ScholarPubMed
Perez, GO, Epstein, M, Rietberg, B & Loutzenhiser, R (1978) Metabolism of arginine by the isolated perfused rat kidney. American Journal of Physiology 235, F376F380.Google ScholarPubMed
Poeze, M, Greve, JW & Ramsay, G (1999) Oxygen delivery in septic shock. Chest 116, 1145.CrossRefGoogle ScholarPubMed
Porembska, Z, Luboinski, G, Chrzanowska, A, Mielczarek, M, Magnuska, J & Baranczyk-Kuzma, A (2003) Arginase in patients with breast cancer. Clinica Chimica Acta 328, 105111.CrossRefGoogle ScholarPubMed
Preiser, JC, De Backer, D & Vincent, JL (2003) Nitroglycerin for septic shock. Lancet 361, 880.CrossRefGoogle ScholarPubMed
Preli, RB, Klein, KP & Herrington, DM (2002) Vascular effects of dietary L -arginine supplementation. Atherosclerosis 162, 115.CrossRefGoogle ScholarPubMed
Prior, BM, Lloyd, PG, Ren, J, Li, Z, Yang, HT, Laughlin, MH & Terjung, RL (2003) Arteriogenesis: role of nitric oxide. Endothelium 10, 207216.CrossRefGoogle ScholarPubMed
Rao, VL, Audet, RM & Butterworth, RF (1995) Increased nitric oxide synthase activities and L -[ 3H]arginine uptake in brain following portacaval anastomosis. Journal of Neurochemistry 65, 677678.Google ScholarPubMed
Rao, VL, Audet, RM & Butterworth, RF (1997) Increased neuronal nitric oxide synthase expression in brain following portacaval anastomosis. Brain Research 765, 169172.CrossRefGoogle ScholarPubMed
Reade, MC, Clark, MF, Young, JD & Boyd, CA (2002) Increased cationic amino acid flux through a newly expressed transporter in cells overproducing nitric oxide from patients with septic shock. Clinical Science (London) 102, 645650.CrossRefGoogle ScholarPubMed
Rekka, EA & Chrysselis, MC (2002) Nitric oxide in atherosclerosis. Mini Reviews in Medicinal Chemistry 2, 585593.CrossRefGoogle ScholarPubMed
Rettura, G, Padawer, J, Barbul, A, Levenson, SM & Seifter, E (1979) Supplemental arginine increases thymic cellularity in normal and murine sarcoma virus-inoculated mice and increases the resistance to murine sarcoma virus tumor. Journal of Parenteral and Enteral Nutrition 3, 409416.CrossRefGoogle ScholarPubMed
Reynolds, JV, Daly, JM, Shou, J, Sigal, R, Ziegler, MM & Naji, A (1990) Immunologic effects of arginine supplementation in tumor-bearing and non-tumor-bearing hosts. Annals of Surgery 211, 202210.CrossRefGoogle ScholarPubMed
Reynolds, JV, Daly, JM, Zhang, S, Evantash, E, Shou, J, Sigal, R & Ziegler, MM (1988 a) Immunomodulatory mechanisms of arginine. Surgery 104, 142151.Google ScholarPubMed
Reynolds, JV, Thom, AK, Zhang, SM, Ziegler, MM, Naji, A & Daly, JM (1988 b) Arginine, protein malnutrition, and cancer. Journal of Surgical Research 45, 513522.CrossRefGoogle ScholarPubMed
Riso, S, Aluffi, P, Brugnani, M, Farinetti, F, Pia, F & D'Andrea, F (2000) Postoperative enteral immunonutrition in head and neck cancer patients. Clinical Nutrition 19, 407412.CrossRefGoogle ScholarPubMed
Rockey, DC (2003) Vascular mediators in the injured liver. Hepatology 37, 412.CrossRefGoogle ScholarPubMed
Rose, WC (1976) Nutrition Classics. Federation Proceedings 8(2) 546–52, June 1949. Amino acid requirements of man. William C. Rose. Nutrition Reviews 34, 307309.CrossRefGoogle Scholar
Rose, WC, Oesterling, MJ & Womack, M (1948) Comparative growth on diets containing ten and nineteen amino acids, with further observations on the role of glutamic and aspartic acids. Journal of Biological Chemistry 176, 753762.CrossRefGoogle Scholar
Roth, E (1998) L -Arginine-nitric oxide metabolism. Clinical Nutrition 17, 12.CrossRefGoogle Scholar
Santak, B, Radermacher, P, Iber, T, Adler, J, Wachter, U, Vassilev, D, Georgieff, M & Vogt, J (1997) In vivo quantification of endotoxin-induced nitric oxide production in pigs from Na15 NO3 -infusion. British Journal of Pharmacology 122, 16051610.CrossRefGoogle ScholarPubMed
Sarela, AI, Mihaimeed, FM, Batten, JJ, Davidson, BR & Mathie, RT (1999) Hepatic and splanchnic nitric oxide activity in patients with cirrhosis. Gut 44, 749753.CrossRefGoogle ScholarPubMed
Schaffer, MR, Tantry, U, Thornton, FJ & Barbul, A (1999) Inhibition of nitric oxide synthesis in wounds: pharmacology and effect on accumulation of collagen in wounds in mice. European Journal of Surgery 165, 262267.Google ScholarPubMed
Schaffer, MR, Tantry, U, van Wesep, RA & Barbul, A (1997) Nitric oxide metabolism in wounds. Journal of Surgical Research 71, 2531.CrossRefGoogle ScholarPubMed
Scheppach, W, Loges, C, Bartram, P, Christl, SU, Richter, F, Dusel, G, Stehle, P, Furst, P & Kaspar, H (1994) Effect of free glutamine and alanyl-glutamine dipeptide on mucosal proliferation of the human ileum and colon. Gastroenterology 107, 429434.CrossRefGoogle ScholarPubMed
Schutte, H, Mayer, K, Gessler, T, Ruhl, M, Schlaudraff, J, Burger, H, Seeger, W & Grimminger, F (1998) Nitric oxide biosynthesis in an exotoxin-induced septic lung model: role of cNOS and impact on pulmonary hemodynamics. American Journal of Respiratory and Critical Care Medicine 157, 498504.CrossRefGoogle Scholar
Schwartz, D, Schwartz, IF, Gnessin, E, Wollman, Y, Chernichovsky, T, Blum, M & Iaina, A (2003) Differential regulation of glomerular arginine transporters (CAT-1 and CAT-2) in lipopolysaccharide-treated rats. American Journal of Physiology 284, F788F795.Google ScholarPubMed
Scott, JA, Mehta, S, Duggan, M, Bihari, A & McCormack, DG (2002) Functional inhibition of constitutive nitric oxide synthase in a rat model of sepsis. American Journal of Respiratory and Critical Care Medicine 165, 14261432.CrossRefGoogle Scholar
Seifter, E, Rettura, G, Barbul, A & Levenson, SM (1978) Arginine: an essential amino acid for injured rats. Surgery 84, 224230.Google ScholarPubMed
Shah, V, Toruner, M, Haddad, F, Cadelina, G, Papapetropoulos, A, Choo, K, Sessa, WC & Groszmann, RJ (1999) Impaired endothelial nitric oxide synthase activity associated with enhanced caveolin binding in experimental cirrhosis in the rat. Gastroenterology 117, 12221228.CrossRefGoogle ScholarPubMed
Shashidharan, M, Lin, KM, Ternent, CA, Smyrk, TC, Thorson, AG, Blatchford, GJ & Christensen, MA (1999) Influence of arginine dietary supplementation on healing colonic anastomosis in the rat. Diseases of the Colon and Rectum 42, 16131617.CrossRefGoogle ScholarPubMed
Shi, HP, Efron, DT, Most, D, Tantry, US & Barbul, A (2000) Supplemental dietary arginine enhances wound healing in normal but not inducible nitric oxide synthase knockout mice. Surgery 128, 374378.CrossRefGoogle Scholar
Shi, HP, Most, D, Efron, DT, Tantry, U, Fischel, MH & Barbul, A (2001) The role of iNOS in wound healing. Surgery 130, 225229.CrossRefGoogle ScholarPubMed
Sigal, RK, Shou, J & Daly, JM (1992) Parenteral arginine infusion in humans: nutrient substrate or pharmacologic agent? Journal of Parenteral and Enteral Nutrition 16, 423428.CrossRefGoogle ScholarPubMed
Strand, OA, Leone, A, Giercksky, KE & Kirkeboen, KA (2000) Nitric oxide indices in human septic shock. Critical Care Medicine 28, 27792785.CrossRefGoogle ScholarPubMed
Stuehr, DJ & Nathan, CF (1989) Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. Journal of Experimental Medicine 169, 15431555.CrossRefGoogle ScholarPubMed
Suer Gokmen, S, Yoruk, Y, Cakir, E, Yorulmaz, F & Gulen, S (1999) Arginase and ornithine, as markers in human non-small cell lung carcinoma. Cancer Biochemistry Biophysics 17, 125131.Google ScholarPubMed
Sukumar, P, Loo, A, Magur, E, Nandi, J, Oler, A & Levine, RA (1997) Dietary supplementation of nucleotides and arginine promotes healing of small bowel ulcers in experimental ulcerative ileitis. Digestive Diseases and Sciences 42, 15301536.CrossRefGoogle ScholarPubMed
Symeonides, S & Balk, RA (1999) Nitric oxide in the pathogenesis of sepsis. Infectious Disease Clinics of North America 13, 449463.CrossRefGoogle ScholarPubMed
Szabo, C (1996) The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 6, 7988.CrossRefGoogle ScholarPubMed
Szende, B, Tyihak, E & Trezl, L (2001) Role of arginine and its methylated derivatives in cancer biology and treatment. Cancer Cell International 1, 3.CrossRefGoogle ScholarPubMed
Tachibana, K, Mukai, K, Hiraoka, I, Moriguchi, S, Takama, S & Kishino, Y (1985) Evaluation of the effect of arginine-enriched amino acid solution on tumor growth. Journal of Parenteral and Enteral Nutrition 9, 428434.CrossRefGoogle ScholarPubMed
Tajiri, K, Miyakawa, H, Izumi, N, Marumo, F & Sato, C (1995) Systemic hypotension and diuresis by L -arginine in cirrhotic patients with ascites: role of nitric oxide. Hepatology 22, 14301435.Google ScholarPubMed
Takeda, Y, Tominaga, T, Tei, N, Kitamura, M & Taga, S (1975) Inhibitory effect of L -arginine on growth of rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene. Cancer Research 35, 23902393.Google Scholar
Tamir, S, Burney, S & Tannenbaum, SR (1996) DNA damage by nitric oxide. Chemical Research in Toxicology 9, 821827.CrossRefGoogle ScholarPubMed
Tentolouris, C, Tousoulis, D, Goumas, G, Stefanadis, C, Davies, G & Toutouzas, P (2000) L -Arginine in coronary atherosclerosis. International Journal of Cardiology 75, 123128.CrossRefGoogle ScholarPubMed
Thomsen, LL, Miles, DW, Happerfield, L, Bobrow, LG, Knowles, RG & Moncada, S (1995) Nitric oxide synthase activity in human breast cancer. British Journal of Cancer 72, 4144.CrossRefGoogle ScholarPubMed
Tietge, UJ, Bahr, MJ, Manns, MP & Boker, KH (2002) Plasma amino acids in cirrhosis and after liver transplantation: influence of liver function, hepatic hemodynamics and circulating hormones. Clinical Transplantation 16, 917.CrossRefGoogle ScholarPubMed
Titheradge, MA (1999) Nitric oxide in septic shock. Biochimica et Biophysica Acta 1411, 437455.CrossRefGoogle ScholarPubMed
Tizianello, A, de Ferrari, G, Garibotto, G, Guerreri, G & Robaudo, C (1980) Renal metabolism of amino acids and ammonia in subjects with normal renal function and in patients with chronic renal insufficiency. Journal of Clinical Investigations 65, 11621173.CrossRefGoogle ScholarPubMed
Tizianello, A, Deferrari, G, Garibotto, G, Robaudo, C, Salvidio, G & Saffiotti, S (1985) Renal ammoniagenesis in the postprandial period. Contributions to Nephrology 47, 4457.CrossRefGoogle ScholarPubMed
Tousoulis, D, Antoniades, C, Tentolouris, C, Goumas, G, Stefanadis, C & Toutouzas, P (2002) L -Arginine in cardiovascular disease: dream or reality? Vascular Medicine 7, 203211.CrossRefGoogle ScholarPubMed
Tschugguel, W, Schneeberger, C, Unfried, G, Czerwenka, K, Weninger, W, Mildner, M, Gruber, DM, Sator, MO, Waldhor, T & Huber, JC (1999) Expression of inducible nitric oxide synthase in human breast cancer depends on tumor grade. Breast Cancer Research and Treatment 56, 145151.CrossRefGoogle ScholarPubMed
Tzeng, E & Billiar, TR (1997) Nitric oxide and the surgical patient. Archives of Surgery 132, 977982.CrossRefGoogle ScholarPubMed
Ulibarri, JA, Mozdziak, PE, Schultz, E, Cook, C & Best, TM (1999) Nitric oxide donors, sodium nitroprusside and S-nitroso-N-acetylpencillamine, stimulate myoblast proliferation in vitro. In Vitro Cellular and Development Biology. Animal 35, 215218.CrossRefGoogle ScholarPubMed
Unno, N, Wang, H, Menconi, MJ, Tytgat, SH, Larkin, V, Smith, M, Morin, MJ, Chavez, A, Hodin, RA & Fink, MP (1997) Inhibition of inducible nitric oxide synthase ameliorates endotoxin-induced gut mucosal barrier dysfunction in rats. Gastroenterology 113, 12461257.CrossRefGoogle ScholarPubMed
Vakkala, M, Kahlos, K, Lakari, E, Paakko, P, Kinnula, V & Soini, Y (2000) Inducible nitric oxide synthase expression, apoptosis, and angiogenesis in in situ and invasive breast carcinomas. Clinical Cancer Research 6, 24082416.Google ScholarPubMed
Vallance, P, Leone, A, Calver, A, Collier, J & Moncada, S (1992) Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis. Journal of Cardiovascular Pharmacology 20, Suppl. 12, S60S62.CrossRefGoogle ScholarPubMed
Vallance, P & Moncada, S (1991) Hyperdynamic circulation in cirrhosis: a role for nitric oxide? Lancet 337, 776778.CrossRefGoogle ScholarPubMed
van Bokhorst-de van der Schueren, MA, Quak, JJ, von Blomberg van der Flier, BM, Kuik, DJ, Langendoen, SI, Snow, GB, Green, CJ & van Leeuwen, PA (2001) Effect of perioperative nutrition, with and without arginine supplementation, on nutritional status, immune function, postoperative morbidity, and survival in severely malnourished head and neck cancer patients. American Journal of Clinical Nutrition 73, 323332.CrossRefGoogle ScholarPubMed
van der Hulst, RR, von Meyenfeldt, MF, Deutz, NE & Soeters, PB (1997) Glutamine extraction by the gut is reduced in depleted [corrected] patients with gastrointestinal cancer. Annals of Surgery 225, 112121.CrossRefGoogle ScholarPubMed
van der Hulst, RRWJ, Deutz, NEP, von Meyenfeldt, MF, Elbers, JMH, Stockbrugger, RW & Soeters, PB (1994) Decrease of mucosal glutamine concentration in the nutritionally depleted patient. Clinical Nutrition 13, 228233.CrossRefGoogle ScholarPubMed
van der Hulst, RRWJ, van Kreel, BK, von Meyenfeldt, MF, Brummer, R-JM, Arends, J-W, Deutz, NEP & Soeters, PB (1993) Glutamine and the preservation of gut integrity. Lancet 341, 13631365.CrossRefGoogle ScholarPubMed
Vincent, JL, Zhang, H, Szabo, C & Preiser, JC (2000) Effects of nitric oxide in septic shock. American Journal of Respiratory and Critical Care Medicine 161, 17811785.CrossRefGoogle ScholarPubMed
Visek, WJ (1986) Arginine needs, physiological state and usual diets. A reevaluation. Journal of Nutrition 116, 3646.CrossRefGoogle Scholar
Wakabayashi, Y, Yamada, E, Yoshida, T & Takahashi, N (1995) Effect of intestinal resection and arginine-free diet on rat physiology. American Journal of Physiology 269, G313G318.Google ScholarPubMed
Wang, J, Torbenson, M, Wang, Q, Ro, JY & Becich, M (2003) Expression of inducible nitric oxide synthase in paired neoplastic and non-neoplastic primary prostate cell cultures and prostatectomy specimen. Urologic Oncology 21, 117122.CrossRefGoogle ScholarPubMed
Weller, R (2003) Nitric oxide: a key mediator in cutaneous physiology. Clinical and Experimental Dermatology 28, 511514.CrossRefGoogle ScholarPubMed
Wenzel, U, Kuntz, S, De Sousa, UJ & Daniel, H (2003) Nitric oxide suppresses apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions. International Journal of Cancer 106, 666675.CrossRefGoogle ScholarPubMed
Wernerman, J (1998) Glutamine-containing TPN: a question of life and death for intensive care unit-patients? Clinical Nutrition 17, 36.CrossRefGoogle ScholarPubMed
White, MF (1985) The transport of cationic amino acids across the plasma membrane of mammalian cells. Biochimica et Biophysica Acta 822, 355374.CrossRefGoogle ScholarPubMed
Windmueller, HG & Spaeth, AE (1975) Intestinal metabolism of glutamine and glutamate from the lumen as compared to glutamine from blood. Archives of Biochemistry and Biophysics 171, 662672.CrossRefGoogle ScholarPubMed
Windmueller, HG & Spaeth, AE (1976) Metabolism of absorbed aspartate, asparagine, and arginine by rat small intestine in vivo. Archives of Biochemistry and Biophysics 175, 670676.CrossRefGoogle ScholarPubMed
Windmueller, HG & Spaeth, AE (1978) Identification of ketone bodies and glutamine as the major respiratory fuels in vivo for postabsorptive rat small intestine. Journal of Biological Chemistry 253, 6976.CrossRefGoogle ScholarPubMed
Windmueller, HG & Spaeth, AE (1981) Source and fate of circulating citrulline. American Journal of Physiology 241, E473E480.Google ScholarPubMed
Wink, DA, Cook, JA, Pacelli, R, DeGraff, W, Gamson, J, Liebmann, J, Krishna, MC & Mitchell, JB (1996) The effect of various nitric oxide-donor agents on hydrogen peroxide-mediated toxicity: a direct correlation between nitric oxide formation and protection. Archives of Biochemistry and Biophysics 331, 241248.CrossRefGoogle ScholarPubMed
Wink, DA, Vodovotz, Y, Laval, J, Laval, F, Dewhirst, MW & Mitchell, JB (1998) The multifaceted roles of nitric oxide in cancer. Carcinogenesis 19, 711721.CrossRefGoogle ScholarPubMed
Witte, MB & Barbul, A (2002) Role of nitric oxide in wound repair. American Journal of Surgery 183, 406412.CrossRefGoogle ScholarPubMed
Witte, MB, Barbul, A, Schick, MA, Vogt, N & Becker H, D (2002 a) Upregulation of arginase expression in wound-derived fibroblasts. Journal of Surgical Research 105, 3542.CrossRefGoogle ScholarPubMed
Witte, MB, Kiyama, T & Barbul, A (2002 b) Nitric oxide enhances experimental wound healing in diabetes. British Journal of Surgery 89, 15941601.CrossRefGoogle ScholarPubMed
Witte, MB, Thornton, FJ, Tantry, U & Barbul, A (2002 c) L -Arginine supplementation enhances diabetic wound healing: involvement of the nitric oxide synthase and arginase pathways. Metabolism 51, 12691273.CrossRefGoogle ScholarPubMed
Wolf, H, Haeckel, C & Roessner, A (2000) Inducible nitric oxide synthase expression in human urinary bladder cancer. Virchows Archiv 437, 662666.CrossRefGoogle ScholarPubMed
Wu, G & Morris, SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochemical Journal 336, 117.CrossRefGoogle ScholarPubMed
Xia, Y, Dawson, VL, Dawson, TM, Snyder, SH & Zweier, JL (1996) Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury. Proceedings of the National Academy of Sciences USA 93, 67706774.CrossRefGoogle ScholarPubMed
Yagnik, GP, Takahashi, Y, Tsoulfas, G, Reid, K, Murase, N & Geller, DA (2002) Blockade of the L -arginine/NO synthase pathway worsens hepatic apoptosis and liver transplant preservation injury. Hepatology 36, 573581.CrossRefGoogle Scholar
Yeatman, TJ, Risley, GL & Brunson, ME (1991) Depletion of dietary arginine inhibits growth of metastatic tumor. Archives of Surgery 126,1376–1381, discussion 13811382.CrossRefGoogle ScholarPubMed
Yeh, CL, Yeh, SL, Lin, MT & Chen, WJ (2002) Effects of arginine-enriched total parenteral nutrition on inflammatory-related mediator and T-cell population in septic rats. Nutrition 18, 631635.CrossRefGoogle ScholarPubMed
Yoshie, Y & Ohshima, H (1997) Nitric oxide synergistically enhances DNA strand breakage induced by polyhydroxyaromatic compounds, but inhibits that induced by the Fenton reaction. Archives of Biochemistry and Biophysics 342, 1321.CrossRefGoogle ScholarPubMed
Young, VR & Yu, Y-M (1996) Protein and Amino Acid Metabolism Chapter 6. Boston, MA: Little Brown and Company.Google Scholar
Zhuang, JC, Wright, TL, deRojas-Walker, T, Tannenbaum, SR, Wogan, GN (2000) Nitric oxide-induced mutations in the HPRT gene of human lymphoblastoid TK6 cells and in Salmonella typhimurium. Environmental and Molecular Mutagenesis 35, 3947.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
Zimmermann, K, Opitz, N, Dedio, J, Renne, CMuller-Esterl, W & Oess, S (2002) NOSTRIN: a protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase. Proceedings of the National Academy of Sciences USA 99, 1716717172.CrossRefGoogle ScholarPubMed