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The L-Arginine: Nitric Oxide Pathway in Physiology and Pathology

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Cellular and Molecular Biology of Atherosclerosis

Part of the book series: Argenteuil Symposia ((ARGENTEUIL))

Abstract

The demonstration that vascular endothelial cells form nitric oxide (NO) from the amino acid L-arginine has led to the discovery that this molecule not only explains the biological properties of the so-called endothelium-derived relaxing factor (EDRF) but is also the stimulator of the soluble guanylate cyclase in a number of tissues such as the platelet and the brain. Furthermore, NO is a cytotoxic factor released by activated murine macrophages and other cells. NO is synthesized by an enzyme, NO synthase, of which two types have been identified, one constitutive and the other induced by cytokines.

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References

  • Aisaka K, Gross SS, Griffith OW, Levi R (1989) N G-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 160:881–886

    Article  PubMed  CAS  Google Scholar 

  • Amber IJ, Hibbs JB Jr, Taintor RR, Vavrin Z (1988) The L-arginine dependent effector mechanism is induced in murine adenocarcinoma cells by culture supernatant from cytotoxic activated macrophages. J Leukocyte Biol 43:187–192

    PubMed  CAS  Google Scholar 

  • Amezcua JL, Dusting GJ, Palmer RMJ, Moncada S (1988) Acetylcholine induces vasodilatation in the rabbit isolated heart through the release of nitric oxide, the endogenous nitrovasodilator. Br J Pharmacol 95:830–834

    PubMed  CAS  Google Scholar 

  • Amezcua JL, Palmer RMJ, de Souza BM, Moncada S (1989) Nitric oxide synthesized from L-arginine regulates vascular tone in the coronary circulation of the rabbit. Br J Pharmacol 97:1119–1124

    PubMed  CAS  Google Scholar 

  • Ashley RH, Brammer MJ, Marchbanks R (1984) Measurement of intrasynaptosomal free calcium by using the fluorescent indicator quin-2. Biochem J 219:149–158

    PubMed  CAS  Google Scholar 

  • Azuma H, Ishikawa M, Sekizaki S (1986) Endothelium-dependent inhibition of platelet aggregation. Br J Pharmacol 88:411–415

    PubMed  CAS  Google Scholar 

  • Billiar TR, Curran RD, Stuehr DJ, West MA, Bentz BG, Simmons RL (1989) An L-arginine dependent mechanism mediates Kupffer cell inhibition of hepatocyte protein synthesis in vitro. J Exp Med 169:1467–1472

    Article  PubMed  CAS  Google Scholar 

  • Billiar TR, Curran RD, Stuehr DJ, Stadler J, Simmons RL, Murray SA (1990a) Inducible cytosolic enzyme activity for the production of nitrogen oxides from L-arginine in hepatocytes. Biochem Biophys Res Commun 168:1034–1040

    Article  PubMed  CAS  Google Scholar 

  • Billiar TR, Curran RD, Stuehr DJ, Hofmann K, Simmons RL (1990b) Inhibition of L-arginine metabolism by N G-monomethyl-L-arginine in vivo promotes hepatic damage in response to lipopolysaccharide. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 275–280

    Google Scholar 

  • Bredt DS, Snyder SH (1989) Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci USA 86:9030–9033

    Article  PubMed  CAS  Google Scholar 

  • Bredt DS, Snyder SH (1990) Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci USA 87:682–685

    Article  PubMed  CAS  Google Scholar 

  • Broten TP, Miyashiro JK, Feigl EO, Moncada S (1991) The role of EDRF in parasympathetic cholinergic coronary vasodilatation. Circulation (submitted)

    Google Scholar 

  • Chen WZ, Palmer RMJ, Moncada S (1989) The release of nitric oxide from the rabbit aorta. J Vasc Med Biol 1:2–6

    Google Scholar 

  • Chu A, Lin C-C, Chambers DE, Kuehl WD, Palmer RMJ, Moncada S, Cobb FR (1991) Effects of inhibition of nitric oxide formation on basal tone and endothelium-dependent responses of the coronary arteries in awake dogs. J Clin Invest 87:1964–1968

    Article  PubMed  CAS  Google Scholar 

  • Curran RD, Billar TR, Stuehr DJ, Hofmann K, Simmons RL (1989) Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products from Kupffer cells. J Exp Med 170:1769–1774

    Article  PubMed  CAS  Google Scholar 

  • Cynk E, Kondo K, Salvemini D, Sneddon JM, Vane JR (1988) Human nomocytes and neutrophils inhibit platelet aggregation by releasing an EDRF-like factor. J Physiol 407:23P

    Google Scholar 

  • Deguchi T (1977) Endogenous activating factor for guanylate cyclase in synaptosomal-soluble fraction of rat brain. J Biol Chem 252:7617–7619

    PubMed  CAS  Google Scholar 

  • Deguchi T, Yoshioka M (1982) L-Arginine identifed as an endogenous activator for soluble guanylate cyclase from neuroblastoma cells. J Biol Chem 257:10147–10152

    PubMed  CAS  Google Scholar 

  • Derome G, Tseng R, Mercier P, Lemaire I, Lemaire S (1981) Possible muscarinic regulation of catecholamine secretion mediated by cyclic GMP in isolated bovine adrenal chromaffin cells. Biochem Pharmacol 30:855–860

    Article  PubMed  CAS  Google Scholar 

  • Ding AH, Nathan CF, Stuehr DJ (1988) Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. J Immunol 141:2407–2412

    PubMed  CAS  Google Scholar 

  • Di Rosa M, Radomski M, Carnuccio R, Moncada S (1990) Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages. Biochem Biophys Res Commun 172:1246–1252

    Article  PubMed  Google Scholar 

  • Dohi T, Morita K, Tsujimoto A (1983) Effect of sodium azide on catecholamine release from isolated adrenal gland and on guanylate cyclase. Eur J Pharmacol 94:331–335

    Article  PubMed  CAS  Google Scholar 

  • Fleming I, Gray GA, Julou-Schaeffer G, Parratt JR, Stoclet J-C (1990) Incubation with endotoxin activates the L-arginine pathway in vascular tissue. Biochem Biophys Res Commun 171:562–568

    Article  PubMed  CAS  Google Scholar 

  • Fukuto JM, Wood KS, Byrns RE, Ignarro LJ (1990) N G-Amino-L-arginine: a new potent antagonist of L-arginine-mediated endothelium-dependent relaxation. Biochem Biophys Res Commun 168:458–465

    Article  PubMed  CAS  Google Scholar 

  • Furchgott RF (1984) The role of endothelium in the responses of vascular smooth muscle to drugs. Ann Rev Pharmacol Toxicol 24:175–197

    Article  CAS  Google Scholar 

  • Gardiner SM, Compton AM, Bennett T, Palmer RMJ, Moncada S (1990a) Regional haemodynamic effects of inhibiting endothelial cell production of nitric oxide with N G-monomethyl-L-arginine in conscious rats. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 81–88

    Google Scholar 

  • Gardiner SM, Compton AM, Bennett T, Palmer RMJ, Moncada S (1990b) Control of regional blood flow by endothelium-derived nitric oxide. Hypertension 15:486–492

    PubMed  CAS  Google Scholar 

  • Gardiner SM, Compton AM, Bennett T, Palmer RMJ, Moncada S (1990c) Persistent haemodynamic changes following prolonged infusions of N G-monomethyl-L-arginine (L-NMMA) in conscious rats. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 489–491

    Google Scholar 

  • Gardiner SM, Compton AM, Bennett T, Palmer RMJ, Moncada S (1990d) Regional haemodynamic changes during oral ingestion of N G-monomethyl-L-arginine or N G-nitro-L-arginine methyl ester in conscious Brattleboro rats. Br J Pharmacol 101:10–12

    PubMed  CAS  Google Scholar 

  • Garthwaite J, Charles SL, Chess-Williams R (1988) Endothelium-derived relaxing factor release on activation of NMD A receptors suggests role as intercellular messenger in the brain. Nature 336:385–388

    Article  PubMed  CAS  Google Scholar 

  • Garthwaite J, Garthwaite G, Palmer RMJ, Moncada S (1989a) NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices. Eur J Pharmacol 172:413–416

    Article  PubMed  CAS  Google Scholar 

  • Garthwaite J, Southam E, Anderton M (1989b) A kainate receptor linked to nitric oxide synthesis from arginine. J Neurochem 53:1952–1954

    Article  PubMed  CAS  Google Scholar 

  • Gorsky LD, Forstermann Y, Ishii K, Murad F (1990) Production of an EDRF-like activity in the cytosol of N1E-115 neuroblastoma cells. FASEB J 4:1494–1500

    PubMed  CAS  Google Scholar 

  • Greisman SE (1982) Experimental Gram-negative bacterial sepsis: optimal methyl-prednisolone requirements for prevention of mortality not preventable by antibiotics alone. Proc Soc Exp Biol Med 170:436–442

    PubMed  CAS  Google Scholar 

  • Haynes RC Jr, Murad F (1985) Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogues; inhibitors of adrenocortical steroid biosynthesis. In: Gilman A, Goodman LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics. Macmillan, New York, 7th edn, pp 1459–1489

    Google Scholar 

  • Hegesh E, Shiloah J (1982) Blood nitrates and infantile methemoglobinemia. Clin Chim Acta 125:107–115

    Article  PubMed  CAS  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. J Immunol 138:550–565

    PubMed  CAS  Google Scholar 

  • Hibbs JB Jr, Taintor RR, Vavrin Z, Rachlin EM (1988) Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157:87–94

    Article  PubMed  CAS  Google Scholar 

  • Hibbs JB Jr, Taintor RR, Vavrin Z, Granger DL, Drapier J-C, Amber IJ, Lancaster JR Jr (1990) Synthesis of nitric oxide from a terminal guanidino nitrogen atom of L-arginine: a molecular mechanism regulating cellular proliferation that targets intracellular iron. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 189–223

    Google Scholar 

  • Hinshaw LB, Archer LT, Beller-Todd BK, Coalson JJ, Flournoy DJ, Passey R, Benjamin B, White GL (1980) Survival of primates in LD100 septic shock following steroid/antibiotic therapy. J Surg Res 28:151–170

    Article  PubMed  CAS  Google Scholar 

  • Hoffman SL, Punjabi NH, Kumala S, Moechtar MA, Pulungsih SP, Rivai AR, Rockhill RC, Woodward TE, Loedin AA (1984) Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone. N Engl J Med 310:82–88

    Article  PubMed  CAS  Google Scholar 

  • Hutcheson IR, Whittle BJR, Boughton-Smith NK (1990) Role of nitric oxide in maintaining vascular integrity in endotoxin-induced acute intestinal damage in the rat. Br J Pharmacol 101:815–820

    PubMed  CAS  Google Scholar 

  • Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84:9265–9269

    Article  PubMed  CAS  Google Scholar 

  • Ishii K, Gorsky LD, Forstermann U, Murad F (1989) Endothelium-derived relaxing factor (EDRF): the endogenous activator of soluble guanylate cyclase in various types of cells. J Appl Cardiol 4:505–512

    Google Scholar 

  • Ishii K, Chang B, Kerwin JF, Huang ZJ, Murad F (1990) N G-Nitro-L-arginine: a potent inhibitor of endothelium-derived relaxing factor formation. Eur J Pharmacol 176:219–223

    Article  PubMed  CAS  Google Scholar 

  • Iyengar R, Stuehr DJ, Marietta MA (1987) Macrophage synthesis of nitrite, nitrate and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad Sci USA 84:6369–6373

    Article  PubMed  CAS  Google Scholar 

  • Kelm M, Schrader J (1988) Nitric oxide release from the isolated guinea pig heart. Eur J Pharmacol 155:313–316

    Article  Google Scholar 

  • Kelm M, Feelisch M, Spahr R, Piper H-M, Noack E, Schrader J (1988) Quantitative and kinetic characterization of nitric oxide and EDRF released from cultured endothelial cells. Biochem Biophys Res Commun 154:236–244

    Article  PubMed  CAS  Google Scholar 

  • Khan MT, Furchgott RF (1987) Additional evidence that endothelium-derived relaxing factor is nitric oxide. In: Rand MJ, Raper C (eds) Pharmacology. Elsevier, New York pp 341–344

    Google Scholar 

  • Kilbourn RG, Gross SS, Jubran A, Adams J, Griffith OW, Levi R, Lodato RF (1990) N G-Methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proc Natl Acad Sci USA 87:3629–3632

    Article  PubMed  CAS  Google Scholar 

  • Knowles RG, Palacios M, Palmer RMJ, Moncada S (1989) Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci USA 86:5159–5162

    Article  PubMed  CAS  Google Scholar 

  • Knowles RG, Palacios M, Palmer RMJ, Moncada S (1990a) Kinetic characteristics of nitric oxide synthase from rat brain. Biochem J 269:207–210

    PubMed  CAS  Google Scholar 

  • Knowles RG, Merrett M, Salter M, Moncada S (1990b) Differential induction of brain, lung and liver nitric oxide synthase by endotoxin in the rat. Biochem J 270:833–836

    PubMed  CAS  Google Scholar 

  • Knowles RG, Salter M, Brooks SL, Moncada S (1990c) Anti-inflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in the lung, liver and aorta of the rat. Biochem Biophys Res Commun 172:1042–1048

    Article  PubMed  CAS  Google Scholar 

  • Kwon NS, Nathan CF, Stuehr DJ (1989) Reduced biopterin as a cofactor in the generation of nitrogen oxides by murine macrophages. J Biol Chem 264:20496–20501

    PubMed  CAS  Google Scholar 

  • Lee DKH, Faunce D, Henry D, Sturm R, Rimele T (1988) Rat polymorphonuclear leukocytes (PMN) increase cGMP levels in rat aorta. FASEB J 2: A518

    Google Scholar 

  • Lepoivre M, Boudbid H, Petit J-F (1989) Antiproliferative activity of γ-interferon combined with hpopolysaccharide on murine adenocarcinoma: dependence on an L-arginine metabolism with production of nitrite and citrulline. Cancer Res 49:1970–1976

    PubMed  CAS  Google Scholar 

  • Lepoivre M, Boudbid H, Petit J-F (1990) Antitumour cytostatic effect of EMT6 cells treated with interferon-γ and lipopolysaccharide. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 415–422

    Google Scholar 

  • Marietta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS (1988) Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 27:8706–8711

    Article  Google Scholar 

  • Mayer B, Schmidt K, Humbert R, Bohme E (1989) Biosynthesis of endothelium-derived relaxing factor: a cytosolic enzyme in porcine aortic endothelial cells Ca2+-dependently converts L-arginine into an activator of soluble guanylyl cyclase. Biochem Biophys Res Commun 164:678–685

    Article  PubMed  CAS  Google Scholar 

  • McCall TB, Boughton-Smith NK, Palmer RMJ, Whittle BJR, Moncada S (1989) Synthesis of nitric oxide from L-arginine by neutrophils: release and interaction with superoxide anion. Biochem J 261:293–296

    PubMed  CAS  Google Scholar 

  • McCall T, Palmer RMJ, Boughton-Smith N, Whittle BJR, Moncada S (1990) The L-arginine:nitric oxide pathway in neutrophils. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 257–265

    Google Scholar 

  • McCall TB, Feelisch M, Palmer RMJ, Moncada S (1991) Identification of N-iminoethyl-L-ornithine as an irreversible inhibitor of nitric oxide synthase in phagocytic cells. Br J Pharmacol 102:234–238

    PubMed  CAS  Google Scholar 

  • McKenna TM (1990) Prolonged exposure of rat aorta to low levels of endotoxin in vitro results in impaired contractility: association with vascular cytokine release. J Clin Invest 86:160–168

    Article  PubMed  CAS  Google Scholar 

  • Miki N, Kawabe Y, Kuriyama K (1977) Activation of cerebral guanylate cyclase by nitric oxide. Biochem Biophys Res Commun 75:851–856

    Article  PubMed  CAS  Google Scholar 

  • Moncada S, Palmer RMJ (1990) The L-arginine:nitric oxide pathway in the vessel wall. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 19–33

    Google Scholar 

  • Moncada S, Radomski MW, Palmer RMJ (1988a) Endothelium-derived relaxing factor: identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem Pharmacol 37:2495–2501

    Article  PubMed  CAS  Google Scholar 

  • Moncada S, Palmer RMJ, Higgs EA (1988b) The discovery of nitric oxide as the endogenous nitrovasodilator. Hypertension 12:365–372

    PubMed  CAS  Google Scholar 

  • Moncada S, Palmer RMJ, Higgs EA (1989) Biosynthesis of nitric oxide from L-arginine: a pathway for the regulation of cell function and communication. Biochem Pharmacol 38:1709–1715

    Article  PubMed  CAS  Google Scholar 

  • Moore PK, al Swayeh OA, Chong NWS, Evans R, Mirzazadeh S, Gibson A (1989) L-N G-Nitroarginine (NOARG) inhibits endothelium-dependent vasodilatation in the rabbit aorta and perfused rat mesentery. Br J Pharmacol 98:905P

    Google Scholar 

  • Mulsch A, Busse R (1990) N G-Nitro-L-arginine (N 5-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. Naunyn-Schmiedebergs Arch Pharmacol 341:143–147

    PubMed  CAS  Google Scholar 

  • Mulsch A, Bassenge E, Busee R (1989) Nitric oxide synthesis in endothelial cytosol: evidence for a calcium-dependent and a calcium-independent mechanism. Naunyn-Schmiedebergs Arch Pharmacol 340:767:770

    PubMed  CAS  Google Scholar 

  • Nicholson DP (1982) Glucocorticoids in the treatment of shock and the adult respiratory distress syndrome. Clin Chest Med 3:121–132

    PubMed  CAS  Google Scholar 

  • Olson DR, Kon C, Breckenridge BM (1976) Calcium ion effects on guanylate cyclase of brain. Life Sci 18:935–940

    Article  PubMed  CAS  Google Scholar 

  • O’Sullivan AJ, Burgoyne RD (1990) Cyclic GMP regulates nicotine-induced secretion from cultured bovine adrenal chromaffin cells: effects of 8-bromo-cyclic GMP, atrial natriuretic peptide, and nitroprusside (nitric oxide). J Neurochem 54:1805–1808

    Article  PubMed  Google Scholar 

  • Palacios M, Knowles RG, Palmer RMJ, Moncada S (1989) Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands. Biochem Biophys Res Commun 165:802–809

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature (Lond) 327:524–526

    Article  CAS  Google Scholar 

  • Palmer RMJ, Ashton DS, Moncada S (1988a) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature (Lond) 333:664–666

    Article  CAS  Google Scholar 

  • Palmer RMJ, Rees DD, Ashton DS, Moncada S (1988b) L-Arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun 153:1251–1256

    Article  PubMed  CAS  Google Scholar 

  • Parratt JR (1973) Myocardial and circulatory effects of E. coli endotoxin; modification of responses to catecholamines. Br J Pharmacol 47: 12–25

    PubMed  CAS  Google Scholar 

  • Perchellet JP, Shanker G, Sharma RK (1978) Regulatory role of guanosine 3′, 5′-monophosphate in adrenocorticotropin hormone-induced steroidogenesis. Science 199:311–312

    Article  PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1987a) Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol 92:181–187

    PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1987b) The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun 148:1482–1489

    Article  PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1987c) The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol 92:639–646

    PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1990a) An L-arginine:nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci USA 87:5193–5197

    Article  PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RMJ, Moncada S (1990b) Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci USA 87:10043–10047

    Article  PubMed  CAS  Google Scholar 

  • Rees DD, Palmer RMJ, Hodson HF, Moncada S (1989a) A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol 96:418–424

    PubMed  CAS  Google Scholar 

  • Rees DD, Palmer RMJ, Moncada S (1989b) Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 86:3375–3378

    Article  PubMed  CAS  Google Scholar 

  • Rees DD, Palmer RMJ, Schulz R, Hodson HF, Moncada S (1990a) Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol 101:746–752

    PubMed  CAS  Google Scholar 

  • Rees DD, Schulz R, Hodson HF, Palmer RMJ, Moncada S (1990b) Identification of some novel inhibitors of the vascular nitric oxide synthase in vivo and in vitro. In: Moncada S, Higgs EA (eds) Nitric oxide from L-arginine: a bioregulatory system. Elsevier, Amsterdam, pp 485–487

    Google Scholar 

  • Rees DD, Cellek S, Palmer RMJ, Moncada S (1990c) Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone: an insight into endotoxin shock. Biochem Biophys Res Commun 173: 541–547

    Article  PubMed  CAS  Google Scholar 

  • Rimele TJ, Sturm RJ, Adams LM, Henry DE, Heaslip RJ, Weichman BM, Grimes D (1988) Interaction of neutrophils with vascular smooth muscle: identification of a neutrophil-derived relaxing factor. J Pharmacol Exp Ther 245:102–111

    PubMed  CAS  Google Scholar 

  • Sakuma I, Stuehr D, Gross SS, Nathan C, Levi R (1988) Identification of arginine as a precursor of endothelium-derived relaxing factor (EDRF). Proc Natl Acad Sci USA 85:8664–8667

    Article  PubMed  CAS  Google Scholar 

  • Salvemini D, De Nucci G, Gryglewski RJ, Vane JR (1989) Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing a nitric oxide-like factor. Proc Natl Acad Sci USA 86:6328–6332

    Article  PubMed  CAS  Google Scholar 

  • Salvemini D, Masini E, Anggard E, Mannaioni PF, Vane JR (1990) Synthesis of a nitric oxide-like factor from L-arginine by rat serosal mast cells: stimulation of guanylate cyclase and inhibition of platelet aggregation. Biochem Biophys Res Commun 169:596–601

    Article  PubMed  CAS  Google Scholar 

  • Schmidt HHHW, Nau H, Wittfoht W, Gerlach J, Prescher K-E, Klein MM, Niroomand F, Bohme E (1988) Arginine is a physiological precursor of endothelium-derived nitric oxide. Eur J Pharmacol 154:213–216

    Article  PubMed  CAS  Google Scholar 

  • Schmidt HHHW, Wilke P, Evers B, Bohme E (1989a) Enzymatic formation of nitrogen oxides from L-arginine in bovine brain cytosol. Biochem Biophys Res Commun 165:284–291

    Article  PubMed  CAS  Google Scholar 

  • Schmidt HHHW, Seifert R, Bohme E (1989b) Formation and release of nitric oxide from human neutrophils and HL-60 cells induced by chemotactic peptide, platelet activating factor and leukotriene B2. FEBS Lett 244:357–360

    Article  PubMed  CAS  Google Scholar 

  • Schroder H, Schror K (1989) Cyclic GMP stimulation by vasopressin in LLC-PK1 kidney epithelial cells is L-arginine-dependent. Naunyn Schmiedebergs Arch Pharmacol 340:475–477

    Article  PubMed  CAS  Google Scholar 

  • Stuehr DJ, Marietta MA (1985) Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc Natl Acad Sci USA 82:7738–7742

    Article  PubMed  CAS  Google Scholar 

  • Stuehr DJ, Marietta MA (1987a) Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines or interferon-γ. J Immunol 139:518–525

    PubMed  CAS  Google Scholar 

  • Stuehr DJ, Marietta MA (1987b) Synthesis of nitrite and nitrate in murine macrophage cell lines. Cancer Res 47:5590–5594

    PubMed  CAS  Google Scholar 

  • Stuehr DJ, Nathan CF (1989) Nitric oxide: a macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 169:1543–1555

    Article  PubMed  CAS  Google Scholar 

  • Stuehr D, Gross S, Sakuma I, Levi R, Nathan C (1989) Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide. J Exp Med 169:1011–1020

    Article  PubMed  CAS  Google Scholar 

  • Stuehr DJ, Kwon NS, Nathan CF (1990) FAD and GSH participate in macrophage synthesis of nitric oxide. Biochem Biophys Res Commun 168:558–565

    Article  PubMed  CAS  Google Scholar 

  • Tayeh MA, Marietta MA (1989) Macrophage oxidation of L-arginine to nitric oxide, nitrite and nitrate. Tetrahydrobiopterin is required as a cofactor. J Biol Chem 264:19654–19658

    PubMed  CAS  Google Scholar 

  • Thiemermann C, Vane J (1990) Inhibition of nitric oxide synthesis reduces the hypotension induced by bacterial lipopolysaccharides in the rat in vivo. Eur J Pharmacol 182:591–595

    Article  PubMed  CAS  Google Scholar 

  • Tolins J, Palmer RMJ, Moncada S, Raij L (1990) Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses. Am J Physiol 258:H655–H662

    PubMed  CAS  Google Scholar 

  • Vallance P, Collier J, Moncada S (1989a) Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 11:997–1000

    Article  Google Scholar 

  • Vallance P, Collier J, Moncada S (1989b) Nitric oxide synthesised from L-arginine mediates endothelium-dependent dilatation in human veins. Cardiovasc Res 23:1053–1057

    Article  PubMed  CAS  Google Scholar 

  • Wagner DA, Young VR, Tannenbaum SR (1983) Mammalian nitrate biosynthesis: incorporation of 15NH3 into nitrate is enhanced by endotoxin treatment. Proc Natl Acad Sci USA 80:4518–4521

    Article  PubMed  CAS  Google Scholar 

  • Wagner DA, Young VR, Tannenbaum SR, Schultz DS, Deen WM (1984) Mammalian nitrate biochemistry: metabolism and endogenous synthesis. In: O’Neill IK, von Borstel RC, Long JE, Miller CT, Martsch H (eds) N-Nitroso compounds: occurrence, biological effects and relevance to human cancer. IARC Scientific Publication no. 57:247–253

    Google Scholar 

  • Wakabayashi I, Hatake K, Kakashita E, Nagai K (1987) Diminution of contractile response of the aorta from endotoxin-injected rats. Eur J Pharmacol 141:117–122

    Article  PubMed  CAS  Google Scholar 

  • Whittle BJR, Lopez-Belmonte J, Rees DD (1989) Modulation of the vasodepressor actions of acetylcholine, bradykinin, substance P and endothelin in the rat by a specific inhibitor of nitric oxide formation. Br J Pharmacol 98:646–652

    PubMed  CAS  Google Scholar 

  • Wood PL, Emmett MR, Rao TS, Cler J, Mick S, Iyengar S (1990) Inhibition of nitric oxide synthase blocks N-methyl-D-aspartate-, quisqualate-, kainate-, harmaline-and pentylenetetrazole-dependent increases in cerebellar cyclic GMP in vivo. J Neurochem 55:346–348

    Article  PubMed  CAS  Google Scholar 

  • Wright DC, Mulsch A, Busse R, Osswald H (1989) Generation of nitric oxide by human neutrophils. Biochem Biophys Res Commun 160:813–819

    Article  PubMed  CAS  Google Scholar 

  • Yoshikawa K, Kuriyama K (1980) Characterization of cerebellar guanylate cyclase using N-methyl-N-nitro-N-nitrosoguanidine: presence of two different types of guanylate cyclase in soluble and particulate fraction. Biochim Biophys Acta 628:377–387

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. S. Moncada
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  2. E. A. Higgs
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Editors and Affiliations

  1. The Methodist Hospital and Baylor College of Medicine, Houston, Texas, 77030, USA

    Antonio M. Gotto Jr MD, DPhil

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© 1992 Springer-Verlag London Limited

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Moncada, S., Higgs, E.A. (1992). The L-Arginine: Nitric Oxide Pathway in Physiology and Pathology. In: Gotto, A.M. (eds) Cellular and Molecular Biology of Atherosclerosis. Argenteuil Symposia. Springer, London. https://doi.org/10.1007/978-1-4471-1909-8_2

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  • DOI: https://doi.org/10.1007/978-1-4471-1909-8_2

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-1911-1

  • Online ISBN: 978-1-4471-1909-8

  • eBook Packages: Springer Book Archive

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