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. 1995 Mar;221(3):220–235. doi: 10.1097/00000658-199503000-00003

The emerging multifaceted roles of nitric oxide.

P C Kuo 1, R A Schroeder 1
PMCID: PMC1234563  PMID: 7717775

Abstract

Nitric oxide (NO) is a highly reactive free radical with a multitude of organ specific regulatory functions. Since 1985, NO has been the subject of numerous research efforts and as a result, has been found to play a major role in the cardiovascular, pulmonary, gastrointestinal, immune, and central nervous systems. In addition, deranged NO synthesis is the basis for a number of pathophysiologic states, such as atherosclerosis, pulmonary hypertension, pyloric stenosis, and the hypertension associated with renal failure. Traditional NO donors such as sodium nitroprusside and new pharmacologic NO adducts such as S-nitrosothiols may serve as exogenous sources of NO for the treatment of NO-deficient pathologic states. This review is an attempt to acquaint the surgical community with the fundamentals of NO biochemistry and physiology. Increased knowledge of its functions in normal homeostasis and pathologic states will enable physicians to better understand these disease processes and utilize new pharmacologic therapies.

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Selected References

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  1. Adams L. B., Hibbs J. B., Jr, Taintor R. R., Krahenbuhl J. L. Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. J Immunol. 1990 Apr 1;144(7):2725–2729. [PubMed] [Google Scholar]
  2. Aoki E., Semba R., Mikoshiba K., Kashiwamata S. Predominant localization in glial cells of free L-arginine. Immunocytochemical evidence. Brain Res. 1991 May 3;547(2):190–192. doi: 10.1016/0006-8993(91)90961-t. [DOI] [PubMed] [Google Scholar]
  3. Barnes P. J. Nitric oxide and airways. Eur Respir J. 1993 Feb;6(2):163–165. [PubMed] [Google Scholar]
  4. Bauer M. L., Beckman J. S., Bridges R. J., Fuller C. M., Matalon S. Peroxynitrite inhibits sodium uptake in rat colonic membrane vesicles. Biochim Biophys Acta. 1992 Feb 17;1104(1):87–94. doi: 10.1016/0005-2736(92)90135-9. [DOI] [PubMed] [Google Scholar]
  5. Beckman J. S., Beckman T. W., Chen J., Marshall P. A., Freeman B. A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620–1624. doi: 10.1073/pnas.87.4.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beckman J. S., Crow J. P. Pathological implications of nitric oxide, superoxide and peroxynitrite formation. Biochem Soc Trans. 1993 May;21(2):330–334. doi: 10.1042/bst0210330. [DOI] [PubMed] [Google Scholar]
  7. Beckman J. S. The double-edged role of nitric oxide in brain function and superoxide-mediated injury. J Dev Physiol. 1991 Jan;15(1):53–59. [PubMed] [Google Scholar]
  8. Belvisi M. G., Stretton C. D., Yacoub M., Barnes P. J. Nitric oxide is the endogenous neurotransmitter of bronchodilator nerves in humans. Eur J Pharmacol. 1992 Jan 14;210(2):221–222. doi: 10.1016/0014-2999(92)90676-u. [DOI] [PubMed] [Google Scholar]
  9. Boughton-Smith N. K., Hutcheson I. R., Deakin A. M., Whittle B. J., Moncada S. Protective effect of S-nitroso-N-acetyl-penicillamine in endotoxin-induced acute intestinal damage in the rat. Eur J Pharmacol. 1990 Dec 4;191(3):485–488. doi: 10.1016/0014-2999(90)94185-z. [DOI] [PubMed] [Google Scholar]
  10. Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
  11. Buchanan J. E., Phillis J. W. The role of nitric oxide in the regulation of cerebral blood flow. Brain Res. 1993 May 7;610(2):248–255. doi: 10.1016/0006-8993(93)91408-k. [DOI] [PubMed] [Google Scholar]
  12. Buisson A., Plotkine M., Boulu R. G. The neuroprotective effect of a nitric oxide inhibitor in a rat model of focal cerebral ischaemia. Br J Pharmacol. 1992 Aug;106(4):766–767. doi: 10.1111/j.1476-5381.1992.tb14410.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Burnett A. L., Tillman S. L., Chang T. S., Epstein J. I., Lowenstein C. J., Bredt D. S., Snyder S. H., Walsh P. C. Immunohistochemical localization of nitric oxide synthase in the autonomic innervation of the human penis. J Urol. 1993 Jul;150(1):73–76. doi: 10.1016/s0022-5347(17)35401-0. [DOI] [PubMed] [Google Scholar]
  14. Byrick R. J., Hobbs E. G., Martineau R., Noble W. H. Nitroglycerin relaxes large airways. Anesth Analg. 1983 Apr;62(4):421–425. [PubMed] [Google Scholar]
  15. Böhme G. A., Bon C., Stutzmann J. M., Doble A., Blanchard J. C. Possible involvement of nitric oxide in long-term potentiation. Eur J Pharmacol. 1991 Jul 9;199(3):379–381. doi: 10.1016/0014-2999(91)90505-k. [DOI] [PubMed] [Google Scholar]
  16. Chandler L. J., Beaty B. J., Baldridge G. D., Bishop D. H., Hewlett M. J. Heterologous reassortment of bunyaviruses in Aedes triseriatus mosquitoes and transovarial and oral transmission of newly evolved genotypes. J Gen Virol. 1990 May;71(Pt 5):1045–1050. doi: 10.1099/0022-1317-71-5-1045. [DOI] [PubMed] [Google Scholar]
  17. Chen P. Y., Sanders P. W. L-arginine abrogates salt-sensitive hypertension in Dahl/Rapp rats. J Clin Invest. 1991 Nov;88(5):1559–1567. doi: 10.1172/JCI115467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Clancy R. M., Leszczynska-Piziak J., Abramson S. B. Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase. J Clin Invest. 1992 Sep;90(3):1116–1121. doi: 10.1172/JCI115929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Clancy R. M., Levartovsky D., Leszczynska-Piziak J., Yegudin J., Abramson S. B. Nitric oxide reacts with intracellular glutathione and activates the hexose monophosphate shunt in human neutrophils: evidence for S-nitrosoglutathione as a bioactive intermediary. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3680–3684. doi: 10.1073/pnas.91.9.3680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Dawson V. L., Dawson T. M., Bartley D. A., Uhl G. R., Snyder S. H. Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J Neurosci. 1993 Jun;13(6):2651–2661. doi: 10.1523/JNEUROSCI.13-06-02651.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Dinerman J. L., Lowenstein C. J., Snyder S. H. Molecular mechanisms of nitric oxide regulation. Potential relevance to cardiovascular disease. Circ Res. 1993 Aug;73(2):217–222. doi: 10.1161/01.res.73.2.217. [DOI] [PubMed] [Google Scholar]
  22. Dinh-Xuan A. T. Endothelial modulation of pulmonary vascular tone. Eur Respir J. 1992 Jun;5(6):757–762. [PubMed] [Google Scholar]
  23. Durante W., Schini V. B., Catovsky S., Kroll M. H., Vanhoutte P. M., Schafer A. I. Plasmin potentiates induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells. Am J Physiol. 1993 Feb;264(2 Pt 2):H617–H624. doi: 10.1152/ajpheart.1993.264.2.H617. [DOI] [PubMed] [Google Scholar]
  24. Durante W., Schini V. B., Kroll M. H., Catovsky S., Scott-Burden T., White J. G., Vanhoutte P. M., Schafer A. I. Platelets inhibit the induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells. Blood. 1994 Apr 1;83(7):1831–1838. [PubMed] [Google Scholar]
  25. Endoh M., Maiese K., Pulsinelli W. A., Wagner J. A. Reactive astrocytes express NADPH diaphorase in vivo after transient ischemia. Neurosci Lett. 1993 May 14;154(1-2):125–128. doi: 10.1016/0304-3940(93)90187-p. [DOI] [PubMed] [Google Scholar]
  26. Faraci F. M., Brian J. E., Jr Nitric oxide and the cerebral circulation. Stroke. 1994 Mar;25(3):692–703. doi: 10.1161/01.str.25.3.692. [DOI] [PubMed] [Google Scholar]
  27. Feelisch M., te Poel M., Zamora R., Deussen A., Moncada S. Understanding the controversy over the identity of EDRF. Nature. 1994 Mar 3;368(6466):62–65. doi: 10.1038/368062a0. [DOI] [PubMed] [Google Scholar]
  28. Feigl E. O. EDRF--a protective factor? Nature. 1988 Feb 11;331(6156):490–491. doi: 10.1038/331490a0. [DOI] [PubMed] [Google Scholar]
  29. Finkel M. S., Oddis C. V., Jacob T. D., Watkins S. C., Hattler B. G., Simmons R. L. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science. 1992 Jul 17;257(5068):387–389. doi: 10.1126/science.1631560. [DOI] [PubMed] [Google Scholar]
  30. Flavahan N. A. Atherosclerosis or lipoprotein-induced endothelial dysfunction. Potential mechanisms underlying reduction in EDRF/nitric oxide activity. Circulation. 1992 May;85(5):1927–1938. doi: 10.1161/01.cir.85.5.1927. [DOI] [PubMed] [Google Scholar]
  31. Frostell C. G., Blomqvist H., Hedenstierna G., Lundberg J., Zapol W. M. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology. 1993 Mar;78(3):427–435. doi: 10.1097/00000542-199303000-00005. [DOI] [PubMed] [Google Scholar]
  32. Fukuto J. M., Hszieh R., Gulati P., Chiang K. T., Nagasawa H. T. N,O-diacylated-N-hydroxyarylsulfonamides: nitroxyl precursors with potent smooth muscle relaxant properties. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1367–1373. doi: 10.1016/0006-291x(92)90453-r. [DOI] [PubMed] [Google Scholar]
  33. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  34. Geroulanos S., Schilling J., Cakmakci M., Jung H. H., Largiader F. Inhibition of NO synthesis in septic shock. Lancet. 1992 Feb 15;339(8790):435–435. [PubMed] [Google Scholar]
  35. Granger D. L., Hibbs J. B., Jr, Perfect J. R., Durack D. T. Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages. J Clin Invest. 1988 Apr;81(4):1129–1136. doi: 10.1172/JCI113427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Green S. J., Meltzer M. S., Hibbs J. B., Jr, Nacy C. A. Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. J Immunol. 1990 Jan 1;144(1):278–283. [PubMed] [Google Scholar]
  37. Gruetter C. A., Childers C. E., Bosserman M. K., Lemke S. M., Ball J. G., Valentovic M. A. Comparison of relaxation induced by glyceryl trinitrate, isosorbide dinitrate, and sodium nitroprusside in bovine airways. Am Rev Respir Dis. 1989 May;139(5):1192–1197. doi: 10.1164/ajrccm/139.5.1192. [DOI] [PubMed] [Google Scholar]
  38. Guarner C., Soriano G., Tomas A., Bulbena O., Novella M. T., Balanzo J., Vilardell F., Mourelle M., Moncada S. Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia. Hepatology. 1993 Nov;18(5):1139–1143. [PubMed] [Google Scholar]
  39. Harbrecht B. G., Billiar T. R., Stadler J., Demetris A. J., Ochoa J., Curran R. D., Simmons R. L. Inhibition of nitric oxide synthesis during endotoxemia promotes intrahepatic thrombosis and an oxygen radical-mediated hepatic injury. J Leukoc Biol. 1992 Oct;52(4):390–394. doi: 10.1002/jlb.52.4.390. [DOI] [PubMed] [Google Scholar]
  40. Harrison D. G., Armstrong M. L., Freiman P. C., Heistad D. D. Restoration of endothelium-dependent relaxation by dietary treatment of atherosclerosis. J Clin Invest. 1987 Dec;80(6):1808–1811. doi: 10.1172/JCI113276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Hayashi T., Fukuto J. M., Ignarro L. J., Chaudhuri G. Basal release of nitric oxide from aortic rings is greater in female rabbits than in male rabbits: implications for atherosclerosis. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11259–11263. doi: 10.1073/pnas.89.23.11259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Hedlund P., Holmquist F., Hedlund H., Andersson K. E. Effects of nicorandil on human isolated corpus cavernosum and cavernous artery. J Urol. 1994 Apr;151(4):1107–1113. doi: 10.1016/s0022-5347(17)35193-5. [DOI] [PubMed] [Google Scholar]
  43. Henry Y., Lepoivre M., Drapier J. C., Ducrocq C., Boucher J. L., Guissani A. EPR characterization of molecular targets for NO in mammalian cells and organelles. FASEB J. 1993 Sep;7(12):1124–1134. doi: 10.1096/fasebj.7.12.8397130. [DOI] [PubMed] [Google Scholar]
  44. Hibbs J. B., Jr, Westenfelder C., Taintor R., Vavrin Z., Kablitz C., Baranowski R. L., Ward J. H., Menlove R. L., McMurry M. P., Kushner J. P. Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J Clin Invest. 1992 Mar;89(3):867–877. doi: 10.1172/JCI115666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Hoffman R. A., Langrehr J. M., Billiar T. R., Curran R. D., Simmons R. L. Alloantigen-induced activation of rat splenocytes is regulated by the oxidative metabolism of L-arginine. J Immunol. 1990 Oct 1;145(7):2220–2226. [PubMed] [Google Scholar]
  46. Holmquist F., Hedlund H., Andersson K. E. L-NG-nitro arginine inhibits non-adrenergic, non-cholinergic relaxation of human isolated corpus cavernosum. Acta Physiol Scand. 1991 Mar;141(3):441–442. doi: 10.1111/j.1748-1716.1991.tb09103.x. [DOI] [PubMed] [Google Scholar]
  47. Hope B. T., Michael G. J., Knigge K. M., Vincent S. R. Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2811–2814. doi: 10.1073/pnas.88.7.2811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Hutcheson I. R., Whittle B. J., Boughton-Smith N. K. Role of nitric oxide in maintaining vascular integrity in endotoxin-induced acute intestinal damage in the rat. Br J Pharmacol. 1990 Dec;101(4):815–820. doi: 10.1111/j.1476-5381.1990.tb14163.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Iadecola C. Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia? Proc Natl Acad Sci U S A. 1992 May 1;89(9):3913–3916. doi: 10.1073/pnas.89.9.3913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Iadecola C., Pelligrino D. A., Moskowitz M. A., Lassen N. A. Nitric oxide synthase inhibition and cerebrovascular regulation. J Cereb Blood Flow Metab. 1994 Mar;14(2):175–192. doi: 10.1038/jcbfm.1994.25. [DOI] [PubMed] [Google Scholar]
  51. Ignarro L. J., Bush P. A., Buga G. M., Wood K. S., Fukuto J. M., Rajfer J. Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun. 1990 Jul 31;170(2):843–850. doi: 10.1016/0006-291x(90)92168-y. [DOI] [PubMed] [Google Scholar]
  52. Ischiropoulos H., Zhu L., Beckman J. S. Peroxynitrite formation from macrophage-derived nitric oxide. Arch Biochem Biophys. 1992 Nov 1;298(2):446–451. doi: 10.1016/0003-9861(92)90433-w. [DOI] [PubMed] [Google Scholar]
  53. Ischiropoulos H., Zhu L., Chen J., Tsai M., Martin J. C., Smith C. D., Beckman J. S. Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys. 1992 Nov 1;298(2):431–437. doi: 10.1016/0003-9861(92)90431-u. [DOI] [PubMed] [Google Scholar]
  54. Iyengar R., Stuehr D. J., Marletta M. A. Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6369–6373. doi: 10.1073/pnas.84.18.6369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. James S. L., Glaven J. Macrophage cytotoxicity against schistosomula of Schistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates. J Immunol. 1989 Dec 15;143(12):4208–4212. [PubMed] [Google Scholar]
  56. Jansen A., Drazen J., Osborne J. A., Brown R., Loscalzo J., Stamler J. S. The relaxant properties in guinea pig airways of S-nitrosothiols. J Pharmacol Exp Ther. 1992 Apr;261(1):154–160. [PubMed] [Google Scholar]
  57. Kaufman H. S., Shermak M. A., May C. A., Pitt H. A., Lillemoe K. D. Nitric oxide inhibits resting sphincter of Oddi activity. Am J Surg. 1993 Jan;165(1):74–80. doi: 10.1016/s0002-9610(05)80407-6. [DOI] [PubMed] [Google Scholar]
  58. Keaney J. F., Jr, Simon D. I., Stamler J. S., Jaraki O., Scharfstein J., Vita J. A., Loscalzo J. NO forms an adduct with serum albumin that has endothelium-derived relaxing factor-like properties. J Clin Invest. 1993 Apr;91(4):1582–1589. doi: 10.1172/JCI116364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Kilbourn R. G., Griffith O. W. Overproduction of nitric oxide in cytokine-mediated and septic shock. J Natl Cancer Inst. 1992 Jun 3;84(11):827–831. doi: 10.1093/jnci/84.11.827. [DOI] [PubMed] [Google Scholar]
  60. Kilbourn R. G., Gross S. S., Jubran A., Adams J., Griffith O. W., Levi R., Lodato R. F. NG-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proc Natl Acad Sci U S A. 1990 May;87(9):3629–3632. doi: 10.1073/pnas.87.9.3629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Kim N., Azadzoi K. M., Goldstein I., Saenz de Tejada I. A nitric oxide-like factor mediates nonadrenergic-noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest. 1991 Jul;88(1):112–118. doi: 10.1172/JCI115266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Kinsella J. P., Neish S. R., Shaffer E., Abman S. H. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet. 1992 Oct 3;340(8823):819–820. doi: 10.1016/0140-6736(92)92687-b. [DOI] [PubMed] [Google Scholar]
  63. Kolb H., Kolb-Bachofen V. Type 1 (insulin-dependent) diabetes mellitus and nitric oxide. Diabetologia. 1992 Aug;35(8):796–797. doi: 10.1007/BF00429103. [DOI] [PubMed] [Google Scholar]
  64. Koppenol W. H., Moreno J. J., Pryor W. A., Ischiropoulos H., Beckman J. S. Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol. 1992 Nov-Dec;5(6):834–842. doi: 10.1021/tx00030a017. [DOI] [PubMed] [Google Scholar]
  65. Kremsner P. G., Nüssler A., Neifer S., Chaves M. F., Bienzle U., Senaldi G., Grau G. E. Malaria antigen and cytokine-induced production of reactive nitrogen intermediates by murine macrophages: no relevance to the development of experimental cerebral malaria. Immunology. 1993 Feb;78(2):286–290. [PMC free article] [PubMed] [Google Scholar]
  66. Kröncke K. D., Kolb-Bachofen V., Berschick B., Burkart V., Kolb H. Activated macrophages kill pancreatic syngeneic islet cells via arginine-dependent nitric oxide generation. Biochem Biophys Res Commun. 1991 Mar 29;175(3):752–758. doi: 10.1016/0006-291x(91)91630-u. [DOI] [PubMed] [Google Scholar]
  67. Kubes P., Kanwar S., Niu X. F., Gaboury J. P. Nitric oxide synthesis inhibition induces leukocyte adhesion via superoxide and mast cells. FASEB J. 1993 Oct;7(13):1293–1299. doi: 10.1096/fasebj.7.13.8405815. [DOI] [PubMed] [Google Scholar]
  68. Kubes P., Suzuki M., Granger D. N. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651–4655. doi: 10.1073/pnas.88.11.4651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Kuo P. C., Slivka A. Nitric oxide decreases oxidant-mediated hepatocyte injury. J Surg Res. 1994 Jun;56(6):594–600. doi: 10.1006/jsre.1994.1094. [DOI] [PubMed] [Google Scholar]
  70. Lancaster J. R., Jr, Langrehr J. M., Bergonia H. A., Murase N., Simmons R. L., Hoffman R. A. EPR detection of heme and nonheme iron-containing protein nitrosylation by nitric oxide during rejection of rat heart allograft. J Biol Chem. 1992 Jun 5;267(16):10994–10998. [PubMed] [Google Scholar]
  71. Langrehr J. M., Hoffman R. A., Lancaster J. R., Jr, Simmons R. L. Nitric oxide--a new endogenous immunomodulator. Transplantation. 1993 Jun;55(6):1205–1212. doi: 10.1097/00007890-199306000-00001. [DOI] [PubMed] [Google Scholar]
  72. Langrehr J. M., Murase N., Markus P. M., Cai X., Neuhaus P., Schraut W., Simmons R. L., Hoffman R. A. Nitric oxide production in host-versus-graft and graft-versus-host reactions in the rat. J Clin Invest. 1992 Aug;90(2):679–683. doi: 10.1172/JCI115911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Lee F. Y., Colombato L. A., Albillos A., Groszmann R. J. Administration of N omega-nitro-L-arginine ameliorates portal-systemic shunting in portal-hypertensive rats. Gastroenterology. 1993 Nov;105(5):1464–1470. doi: 10.1016/0016-5085(93)90152-3. [DOI] [PubMed] [Google Scholar]
  74. Li C. G., Rand M. J. Evidence that part of the NANC relaxant response of guinea-pig trachea to electrical field stimulation is mediated by nitric oxide. Br J Pharmacol. 1991 Jan;102(1):91–94. doi: 10.1111/j.1476-5381.1991.tb12137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Lüscher T. F. Endothelium-derived nitric oxide: the endogenous nitrovasodilator in the human cardiovascular system. Eur Heart J. 1991 Nov;12 (Suppl E):2–11. doi: 10.1093/eurheartj/12.suppl_e.2. [DOI] [PubMed] [Google Scholar]
  76. MacNaughton W. K., Cirino G., Wallace J. L. Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach. Life Sci. 1989;45(20):1869–1876. doi: 10.1016/0024-3205(89)90540-7. [DOI] [PubMed] [Google Scholar]
  77. Macdonald R. L., Weir B. K. A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke. 1991 Aug;22(8):971–982. doi: 10.1161/01.str.22.8.971. [DOI] [PubMed] [Google Scholar]
  78. Malinski T., Bailey F., Zhang Z. G., Chopp M. Nitric oxide measured by a porphyrinic microsensor in rat brain after transient middle cerebral artery occlusion. J Cereb Blood Flow Metab. 1993 May;13(3):355–358. doi: 10.1038/jcbfm.1993.48. [DOI] [PubMed] [Google Scholar]
  79. Marczin N., Papapetropoulos A., Jilling T., Catravas J. D. Prevention of nitric oxide synthase induction in vascular smooth muscle cells by microtubule depolymerizing agents. Br J Pharmacol. 1993 Jul;109(3):603–605. doi: 10.1111/j.1476-5381.1993.tb13613.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
  81. Marsden P. A., Brenner B. M. Nitric oxide and endothelins: novel autocrine/paracrine regulators of the circulation. Semin Nephrol. 1991 Mar;11(2):169–185. [PubMed] [Google Scholar]
  82. Marsden P. A., Heng H. H., Scherer S. W., Stewart R. J., Hall A. V., Shi X. M., Tsui L. C., Schappert K. T. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1993 Aug 15;268(23):17478–17488. [PubMed] [Google Scholar]
  83. Matheis G., Sherman M. P., Buckberg G. D., Haybron D. M., Young H. H., Ignarro L. J. Role of L-arginine-nitric oxide pathway in myocardial reoxygenation injury. Am J Physiol. 1992 Feb;262(2 Pt 2):H616–H620. doi: 10.1152/ajpheart.1992.262.2.H616. [DOI] [PubMed] [Google Scholar]
  84. Mayhan W. G. Role of prostaglandin H2-thromboxane A2 in responses of cerebral arterioles during chronic hypertension. Am J Physiol. 1992 Feb;262(2 Pt 2):H539–H543. doi: 10.1152/ajpheart.1992.262.2.H539. [DOI] [PubMed] [Google Scholar]
  85. Mayhan W. G., Simmons L. K., Sharpe G. M. Mechanism of impaired responses of cerebral arterioles during diabetes mellitus. Am J Physiol. 1991 Feb;260(2 Pt 2):H319–H326. doi: 10.1152/ajpheart.1991.260.2.H319. [DOI] [PubMed] [Google Scholar]
  86. McNamara D. B., Bedi B., Aurora H., Tena L., Ignarro L. J., Kadowitz P. J., Akers D. L. L-arginine inhibits balloon catheter-induced intimal hyperplasia. Biochem Biophys Res Commun. 1993 May 28;193(1):291–296. doi: 10.1006/bbrc.1993.1622. [DOI] [PubMed] [Google Scholar]
  87. Mellouk S., Green S. J., Nacy C. A., Hoffman S. L. IFN-gamma inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by an L-arginine-dependent effector mechanism. J Immunol. 1991 Jun 1;146(11):3971–3976. [PubMed] [Google Scholar]
  88. Michel T., Li G. K., Busconi L. Phosphorylation and subcellular translocation of endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6252–6256. doi: 10.1073/pnas.90.13.6252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Midgley S., Grant I. S., Haynes W. G., Webb D. J. Nitric oxide in liver failure. Lancet. 1991 Dec 21;338(8782-8783):1590–1590. doi: 10.1016/0140-6736(91)92407-s. [DOI] [PubMed] [Google Scholar]
  90. Moncada S., Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec 30;329(27):2002–2012. doi: 10.1056/NEJM199312303292706. [DOI] [PubMed] [Google Scholar]
  91. Moncada S., Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec 30;329(27):2002–2012. doi: 10.1056/NEJM199312303292706. [DOI] [PubMed] [Google Scholar]
  92. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  93. Mulligan M. S., Hevel J. M., Marletta M. A., Ward P. A. Tissue injury caused by deposition of immune complexes is L-arginine dependent. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6338–6342. doi: 10.1073/pnas.88.14.6338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Mülsch A., Mordvintcev P. I., Vanin A. F., Busse R. Formation and release of dinitrosyl iron complexes by endothelial cells. Biochem Biophys Res Commun. 1993 Nov 15;196(3):1303–1308. doi: 10.1006/bbrc.1993.2394. [DOI] [PubMed] [Google Scholar]
  95. Nagafuji T., Matsui T., Koide T., Asano T. Blockade of nitric oxide formation by N omega-nitro-L-arginine mitigates ischemic brain edema and subsequent cerebral infarction in rats. Neurosci Lett. 1992 Dec 7;147(2):159–162. doi: 10.1016/0304-3940(92)90584-t. [DOI] [PubMed] [Google Scholar]
  96. Nakaki T., Hishikawa K., Suzuki H., Saruta T., Kato R. L-arginine-induced hypotension. Lancet. 1990 Sep 15;336(8716):696–696. doi: 10.1016/0140-6736(90)92196-o. [DOI] [PubMed] [Google Scholar]
  97. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  98. Nozaki K., Moskowitz M. A., Maynard K. I., Koketsu N., Dawson T. M., Bredt D. S., Snyder S. H. Possible origins and distribution of immunoreactive nitric oxide synthase-containing nerve fibers in cerebral arteries. J Cereb Blood Flow Metab. 1993 Jan;13(1):70–79. doi: 10.1038/jcbfm.1993.9. [DOI] [PubMed] [Google Scholar]
  99. Nussler A. K., Billiar T. R. Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukoc Biol. 1993 Aug;54(2):171–178. [PubMed] [Google Scholar]
  100. O'Dell T. J., Hawkins R. D., Kandel E. R., Arancio O. Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11285–11289. doi: 10.1073/pnas.88.24.11285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Palmer R. M. The discovery of nitric oxide in the vessel wall. A unifying concept in the pathogenesis of sepsis. Arch Surg. 1993 Apr;128(4):396–401. doi: 10.1001/archsurg.1993.01420160034004. [DOI] [PubMed] [Google Scholar]
  102. Pastor C., Teisseire B., Vicaut E., Payen D. Effects of L-arginine and L-nitro-arginine treatment on blood pressure and cardiac output in a rabbit endotoxin shock model. Crit Care Med. 1994 Mar;22(3):465–469. doi: 10.1097/00003246-199403000-00017. [DOI] [PubMed] [Google Scholar]
  103. Pearl R. G. Inhaled nitric oxide. The past, the present, and the future. Anesthesiology. 1993 Mar;78(3):413–416. [PubMed] [Google Scholar]
  104. Pellat C., Henry Y., Drapier J. C. IFN-gamma-activated macrophages: detection by electron paramagnetic resonance of complexes between L-arginine-derived nitric oxide and non-heme iron proteins. Biochem Biophys Res Commun. 1990 Jan 15;166(1):119–125. doi: 10.1016/0006-291x(90)91919-j. [DOI] [PubMed] [Google Scholar]
  105. Pepke-Zaba J., Higenbottam T. W., Dinh-Xuan A. T., Stone D., Wallwork J. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet. 1991 Nov 9;338(8776):1173–1174. doi: 10.1016/0140-6736(91)92033-x. [DOI] [PubMed] [Google Scholar]
  106. Persson M. G., Gustafsson L. E., Wiklund N. P., Hedqvist P., Moncada S. Endogenous nitric oxide as a modulator of rabbit skeletal muscle microcirculation in vivo. Br J Pharmacol. 1990 Jul;100(3):463–466. doi: 10.1111/j.1476-5381.1990.tb15829.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Petros A., Bennett D., Vallance P. Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet. 1991 Dec 21;338(8782-8783):1557–1558. doi: 10.1016/0140-6736(91)92376-d. [DOI] [PubMed] [Google Scholar]
  108. Petros A., Lamb G., Leone A., Moncada S., Bennett D., Vallance P. Effects of a nitric oxide synthase inhibitor in humans with septic shock. Cardiovasc Res. 1994 Jan;28(1):34–39. doi: 10.1093/cvr/28.1.34. [DOI] [PubMed] [Google Scholar]
  109. Radi R., Beckman J. S., Bush K. M., Freeman B. A. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys. 1991 Aug 1;288(2):481–487. doi: 10.1016/0003-9861(91)90224-7. [DOI] [PubMed] [Google Scholar]
  110. Reif D. W. Delayed production of nitric oxide contributes to NMDA-mediated neuronal damage. Neuroreport. 1993 May;4(5):566–568. doi: 10.1097/00001756-199305000-00026. [DOI] [PubMed] [Google Scholar]
  111. Seidel C. L., LaRochelle J. Venous and arterial endothelia: different dilator abilities in dog vessels. Circ Res. 1987 Apr;60(4):626–630. doi: 10.1161/01.res.60.4.626. [DOI] [PubMed] [Google Scholar]
  112. Shibuki K., Okada D. Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum. Nature. 1991 Jan 24;349(6307):326–328. doi: 10.1038/349326a0. [DOI] [PubMed] [Google Scholar]
  113. Stamler J. S., Jaraki O., Osborne J., Simon D. I., Keaney J., Vita J., Singel D., Valeri C. R., Loscalzo J. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7674–7677. doi: 10.1073/pnas.89.16.7674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  114. Standaert B., Nelen V., Torts K., Denis L., De Smedt E. Screening for prostatic hyperplasia. Lancet. 1991 Nov 2;338(8775):1155–1155. doi: 10.1016/0140-6736(91)92022-t. [DOI] [PubMed] [Google Scholar]
  115. Stark M. E., Szurszewski J. H. Role of nitric oxide in gastrointestinal and hepatic function and disease. Gastroenterology. 1992 Dec;103(6):1928–1949. doi: 10.1016/0016-5085(92)91454-c. [DOI] [PubMed] [Google Scholar]
  116. Stief C. G., Holmquist F., Djamilian M., Krah H., Andersson K. E., Jonas U. Preliminary results with the nitric oxide donor linsidomine chlorhydrate in the treatment of human erectile dysfunction. J Urol. 1992 Nov;148(5):1437–1440. doi: 10.1016/s0022-5347(17)36931-8. [DOI] [PubMed] [Google Scholar]
  117. Thomas G. R., Thiemermann C., Walder C., Vane J. R. The effects of endothelium-dependent vasodilators on cardiac output and their distribution in the anaesthetized rat: a comparison with sodium nitroprusside. Br J Pharmacol. 1988 Nov;95(3):986–992. doi: 10.1111/j.1476-5381.1988.tb11729.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  118. Thomas G., Ramwell P. W. Vascular relaxation mediated by hydroxylamines and oximes: their conversion to nitrites and mechanism of endothelium dependent vascular relaxation. Biochem Biophys Res Commun. 1989 Oct 31;164(2):889–893. doi: 10.1016/0006-291x(89)91542-8. [DOI] [PubMed] [Google Scholar]
  119. Tracey W. R., Nakane M., Pollock J. S., Förstermann U. Nitric oxide synthases in neuronal cells, macrophages and endothelium are NADPH diaphorases, but represent only a fraction of total cellular NADPH diaphorase activity. Biochem Biophys Res Commun. 1993 Sep 15;195(2):1035–1040. doi: 10.1006/bbrc.1993.2148. [DOI] [PubMed] [Google Scholar]
  120. Trifiletti R. R. Neuroprotective effects of NG-nitro-L-arginine in focal stroke in the 7-day old rat. Eur J Pharmacol. 1992 Jul 21;218(1):197–198. doi: 10.1016/0014-2999(92)90168-4. [DOI] [PubMed] [Google Scholar]
  121. Vallance P., Collier J., Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet. 1989 Oct 28;2(8670):997–1000. doi: 10.1016/s0140-6736(89)91013-1. [DOI] [PubMed] [Google Scholar]
  122. Vallance P., Collier J., Moncada S. Nitric oxide synthesised from L-arginine mediates endothelium dependent dilatation in human veins in vivo. Cardiovasc Res. 1989 Dec;23(12):1053–1057. doi: 10.1093/cvr/23.12.1053. [DOI] [PubMed] [Google Scholar]
  123. Vallance P., Leone A., Calver A., Collier J., Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet. 1992 Mar 7;339(8793):572–575. doi: 10.1016/0140-6736(92)90865-z. [DOI] [PubMed] [Google Scholar]
  124. Vanderwinden J. M., Mailleux P., Schiffmann S. N., Vanderhaeghen J. J., De Laet M. H. Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis. N Engl J Med. 1992 Aug 20;327(8):511–515. doi: 10.1056/NEJM199208203270802. [DOI] [PubMed] [Google Scholar]
  125. Vanin A. F. Endothelium-derived relaxing factor is a nitrosyl iron complex with thiol ligands. FEBS Lett. 1991 Sep 2;289(1):1–3. doi: 10.1016/0014-5793(91)80894-9. [DOI] [PubMed] [Google Scholar]
  126. Vedernikov Y. P., Mordvintcev P. I., Malenkova I. V., Vanin A. F. Similarity between the vasorelaxing activity of dinitrosyl iron cysteine complexes and endothelium-derived relaxing factor. Eur J Pharmacol. 1992 Feb 18;211(3):313–317. doi: 10.1016/0014-2999(92)90386-i. [DOI] [PubMed] [Google Scholar]
  127. Vincendeau P., Daulouède S., Veyret B., Darde M. L., Bouteille B., Lemesre J. L. Nitric oxide-mediated cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei. Exp Parasitol. 1992 Nov;75(3):353–360. doi: 10.1016/0014-4894(92)90220-5. [DOI] [PubMed] [Google Scholar]
  128. Walder C. E., Thiemermann C., Vane J. R. Endothelium-derived relaxing factor participates in the increased blood flow in response to pentagastrin in the rat stomach mucosa. Proc Biol Sci. 1990 Sep 22;241(1302):195–200. doi: 10.1098/rspb.1990.0085. [DOI] [PubMed] [Google Scholar]
  129. Wang Q., Paulson O. B., Lassen N. A. Effect of nitric oxide blockade by NG-nitro-L-arginine on cerebral blood flow response to changes in carbon dioxide tension. J Cereb Blood Flow Metab. 1992 Nov;12(6):947–953. doi: 10.1038/jcbfm.1992.131. [DOI] [PubMed] [Google Scholar]
  130. Whittle B. J., Lopez-Belmonte J., Moncada S. Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat. Br J Pharmacol. 1990 Mar;99(3):607–611. doi: 10.1111/j.1476-5381.1990.tb12977.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  131. Zhang Z. G., Chopp M., Zaloga C., Pollock J. S., Förstermann U. Cerebral endothelial nitric oxide synthase expression after focal cerebral ischemia in rats. Stroke. 1993 Dec;24(12):2016–2022. doi: 10.1161/01.str.24.12.2016. [DOI] [PubMed] [Google Scholar]
  132. Zhu L., Gunn C., Beckman J. S. Bactericidal activity of peroxynitrite. Arch Biochem Biophys. 1992 Nov 1;298(2):452–457. doi: 10.1016/0003-9861(92)90434-x. [DOI] [PubMed] [Google Scholar]

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