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. 1995 Nov;4(6):387–396. doi: 10.1155/S0962935195000639

Nitric oxide as a mediator of inflammation?—You had better believe it

Mark J S Miller 1,✉, Matthew B Grisham 2
PMCID: PMC2365674  PMID: 18475670

Abstract

Nitric oxide has enigmatic qualities in inflammation. In order to appreciate the precise contributions of nitric oxide to a pathophysiological process, one must account for enzyme source, coproduction of oxidants and antioxidant defences, time, rate of nitric oxide production, cellular source, peroxynitrite formation and effects on DNA (mutagenesis/apoptosis). We contend that there is ample evidence to consider nitric oxide as a molecular aggressor in inflammation, particularly chronic inflammation. Therapeutic benefit can be achieved by inhibition of inducible nitric oxide synthase and not the donation of additional nitric oxide. Furthermore, there is growing appreciation that nitric oxide and products derived thereof, are critical components linking the increased incidence of cancer in states of chronic inflammation.

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Selected References

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  1. Aiko S., Grisham M. B. Spontaneous intestinal inflammation and nitric oxide metabolism in HLA-B27 transgenic rats. Gastroenterology. 1995 Jul;109(1):142–150. doi: 10.1016/0016-5085(95)90279-1. [DOI] [PubMed] [Google Scholar]
  2. Bartsch H., Hietanen E., Malaveille C. Carcinogenic nitrosamines: free radical aspects of their action. Free Radic Biol Med. 1989;7(6):637–644. doi: 10.1016/0891-5849(89)90144-5. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Beckmann J. S., Ye Y. Z., Anderson P. G., Chen J., Accavitti M. A., Tarpey M. M., White C. R. Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem Hoppe Seyler. 1994 Feb;375(2):81–88. doi: 10.1515/bchm3.1994.375.2.81. [DOI] [PubMed] [Google Scholar]
  6. Boughton-Smith N. K., Evans S. M., Hawkey C. J., Cole A. T., Balsitis M., Whittle B. J., Moncada S. Nitric oxide synthase activity in ulcerative colitis and Crohn's disease. Lancet. 1993 Aug 7;342(8867):338–340. doi: 10.1016/0140-6736(93)91476-3. [DOI] [PubMed] [Google Scholar]
  7. Cho H. J., Xie Q. W., Calaycay J., Mumford R. A., Swiderek K. M., Lee T. D., Nathan C. Calmodulin is a subunit of nitric oxide synthase from macrophages. J Exp Med. 1992 Aug 1;176(2):599–604. doi: 10.1084/jem.176.2.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cross A. H., Misko T. P., Lin R. F., Hickey W. F., Trotter J. L., Tilton R. G. Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates experimental autoimmune encephalomyelitis in SJL mice. J Clin Invest. 1994 Jun;93(6):2684–2690. doi: 10.1172/JCI117282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cui S., Reichner J. S., Mateo R. B., Albina J. E. Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or -independent mechanisms. Cancer Res. 1994 May 1;54(9):2462–2467. [PubMed] [Google Scholar]
  10. Denicola A., Rubbo H., Rodríguez D., Radi R. Peroxynitrite-mediated cytotoxicity to Trypanosoma cruzi. Arch Biochem Biophys. 1993 Jul;304(1):279–286. doi: 10.1006/abbi.1993.1350. [DOI] [PubMed] [Google Scholar]
  11. Doyle M. P., Hoekstra J. W. Oxidation of nitrogen oxides by bound dioxygen in hemoproteins. J Inorg Biochem. 1981 Jul;14(4):351–358. doi: 10.1016/s0162-0134(00)80291-3. [DOI] [PubMed] [Google Scholar]
  12. Drapier J. C., Hibbs J. B., Jr Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells. J Immunol. 1988 Apr 15;140(8):2829–2838. [PubMed] [Google Scholar]
  13. Drapier J. C., Hibbs J. B., Jr Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible. J Clin Invest. 1986 Sep;78(3):790–797. doi: 10.1172/JCI112642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dudek R. R., Wildhirt S., Conforto A., Pinto V., Suzuki H., Winder S., Bing R. J. Inducible nitric oxide synthase activity in myocardium after myocardial infarction in rabbit. Biochem Biophys Res Commun. 1994 Dec 30;205(3):1671–1680. doi: 10.1006/bbrc.1994.2860. [DOI] [PubMed] [Google Scholar]
  15. Elliott S. N., McKnight W., Cirino G., Wallace J. L. A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in rats. Gastroenterology. 1995 Aug;109(2):524–530. doi: 10.1016/0016-5085(95)90341-0. [DOI] [PubMed] [Google Scholar]
  16. Farrell A. J., Blake D. R., Palmer R. M., Moncada S. Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis. 1992 Nov;51(11):1219–1222. doi: 10.1136/ard.51.11.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Granger D. L., Lehninger A. L. Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells. J Cell Biol. 1982 Nov;95(2 Pt 1):527–535. doi: 10.1083/jcb.95.2.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Greenberg S. S., Xie J., Zatarain J. M., Kapusta D. R., Miller M. J. Hydroxocobalamin (vitamin B12a) prevents and reverses endotoxin-induced hypotension and mortality in rodents: role of nitric oxide. J Pharmacol Exp Ther. 1995 Apr;273(1):257–265. [PubMed] [Google Scholar]
  19. Grisham M. B., Specian R. D., Zimmerman T. E. Effects of nitric oxide synthase inhibition on the pathophysiology observed in a model of chronic granulomatous colitis. J Pharmacol Exp Ther. 1994 Nov;271(2):1114–1121. [PubMed] [Google Scholar]
  20. Grisham M. B., Ware K., Gilleland H. E., Jr, Gilleland L. B., Abell C. L., Yamada T. Neutrophil-mediated nitrosamine formation: role of nitric oxide in rats. Gastroenterology. 1992 Oct;103(4):1260–1266. doi: 10.1016/0016-5085(92)91513-4. [DOI] [PubMed] [Google Scholar]
  21. Hewett S. J., Corbett J. A., McDaniel M. L., Choi D. W. Inhibition of nitric oxide formation does not protect murine cortical cell cultures from N-methyl-D-aspartate neurotoxicity. Brain Res. 1993 Oct 22;625(2):337–341. doi: 10.1016/0006-8993(93)91078-7. [DOI] [PubMed] [Google Scholar]
  22. Hibbs J. B., Jr, Taintor R. R., Vavrin Z. Iron depletion: possible cause of tumor cell cytotoxicity induced by activated macrophages. Biochem Biophys Res Commun. 1984 Sep 17;123(2):716–723. doi: 10.1016/0006-291x(84)90288-2. [DOI] [PubMed] [Google Scholar]
  23. Hogaboam C. M., Jacobson K., Collins S. M., Blennerhassett M. G. The selective beneficial effects of nitric oxide inhibition in experimental colitis. Am J Physiol. 1995 Apr;268(4 Pt 1):G673–G684. doi: 10.1152/ajpgi.1995.268.4.G673. [DOI] [PubMed] [Google Scholar]
  24. Huang P. L., Dawson T. M., Bredt D. S., Snyder S. H., Fishman M. C. Targeted disruption of the neuronal nitric oxide synthase gene. Cell. 1993 Dec 31;75(7):1273–1286. doi: 10.1016/0092-8674(93)90615-w. [DOI] [PubMed] [Google Scholar]
  25. Huie R. E., Padmaja S. The reaction of no with superoxide. Free Radic Res Commun. 1993;18(4):195–199. doi: 10.3109/10715769309145868. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Iadecola C., Zhang F., Xu X. Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage. Am J Physiol. 1995 Jan;268(1 Pt 2):R286–R292. doi: 10.1152/ajpregu.1995.268.1.R286. [DOI] [PubMed] [Google Scholar]
  28. Ianaro A., O'Donnell C. A., Di Rosa M., Liew F. Y. A nitric oxide synthase inhibitor reduces inflammation, down-regulates inflammatory cytokines and enhances interleukin-10 production in carrageenin-induced oedema in mice. Immunology. 1994 Jul;82(3):370–375. [PMC free article] [PubMed] [Google Scholar]
  29. Ignarro L. J., Fukuto J. M., Griscavage J. M., Rogers N. E., Byrns R. E. Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8103–8107. doi: 10.1073/pnas.90.17.8103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. Järvinen T. A., Moilanen T., Järvinen T. L., Moilanen E. Nitric oxide mediates interleukin-1 induced inhibition of glycosaminoglycan synthesis in rat articular cartilage. Mediators Inflamm. 1995;4(2):107–111. doi: 10.1155/S0962935195000184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kanwar S., Wallace J. L., Befus D., Kubes P. Nitric oxide synthesis inhibition increases epithelial permeability via mast cells. Am J Physiol. 1994 Feb;266(2 Pt 1):G222–G229. doi: 10.1152/ajpgi.1994.266.2.G222. [DOI] [PubMed] [Google Scholar]
  34. Kaur H., Halliwell B. Evidence for nitric oxide-mediated oxidative damage in chronic inflammation. Nitrotyrosine in serum and synovial fluid from rheumatoid patients. FEBS Lett. 1994 Aug 15;350(1):9–12. doi: 10.1016/0014-5793(94)00722-5. [DOI] [PubMed] [Google Scholar]
  35. King P. A., Jamison E., Strahs D., Anderson V. E., Brenowitz M. 'Footprinting' proteins on DNA with peroxonitrous acid. Nucleic Acids Res. 1993 May 25;21(10):2473–2478. doi: 10.1093/nar/21.10.2473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Koedel U., Bernatowicz A., Paul R., Frei K., Fontana A., Pfister H. W. Experimental pneumococcal meningitis: cerebrovascular alterations, brain edema, and meningeal inflammation are linked to the production of nitric oxide. Ann Neurol. 1995 Mar;37(3):313–323. doi: 10.1002/ana.410370307. [DOI] [PubMed] [Google Scholar]
  37. Kooy N. W., Royall J. A. Agonist-induced peroxynitrite production from endothelial cells. Arch Biochem Biophys. 1994 May 1;310(2):352–359. doi: 10.1006/abbi.1994.1178. [DOI] [PubMed] [Google Scholar]
  38. Kubes P. Nitric oxide-induced microvascular permeability alterations: a regulatory role for cGMP. Am J Physiol. 1993 Dec;265(6 Pt 2):H1909–H1915. doi: 10.1152/ajpheart.1993.265.6.H1909. [DOI] [PubMed] [Google Scholar]
  39. Lindsay R. M., Smith W., Rossiter S. P., McIntyre M. A., Williams B. C., Baird J. D. N omega-nitro-L-arginine methyl ester reduces the incidence of IDDM in BB/E rats. Diabetes. 1995 Mar;44(3):365–368. doi: 10.2337/diab.44.3.365. [DOI] [PubMed] [Google Scholar]
  40. Lipton S. A., Choi Y. B., Pan Z. H., Lei S. Z., Chen H. S., Sucher N. J., Loscalzo J., Singel D. J., Stamler J. S. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature. 1993 Aug 12;364(6438):626–632. doi: 10.1038/364626a0. [DOI] [PubMed] [Google Scholar]
  41. Löwik C. W., Nibbering P. H., van de Ruit M., Papapoulos S. E. Inducible production of nitric oxide in osteoblast-like cells and in fetal mouse bone explants is associated with suppression of osteoclastic bone resorption. J Clin Invest. 1994 Apr;93(4):1465–1472. doi: 10.1172/JCI117124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ma T. T., Ischiropoulos H., Brass C. A. Endotoxin-stimulated nitric oxide production increases injury and reduces rat liver chemiluminescence during reperfusion. Gastroenterology. 1995 Feb;108(2):463–469. doi: 10.1016/0016-5085(95)90075-6. [DOI] [PubMed] [Google Scholar]
  43. McCartney-Francis N., Allen J. B., Mizel D. E., Albina J. E., Xie Q. W., Nathan C. F., Wahl S. M. Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med. 1993 Aug 1;178(2):749–754. doi: 10.1084/jem.178.2.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Middleton S. J., Shorthouse M., Hunter J. O. Increased nitric oxide synthesis in ulcerative colitis. Lancet. 1993 Feb 20;341(8843):465–466. doi: 10.1016/0140-6736(93)90211-x. [DOI] [PubMed] [Google Scholar]
  45. Miller M. J., Munshi U. K., Sadowska-Krowicka H., Kakkis J. L., Zhang X. J., Eloby-Childress S., Clark D. A. Inhibition of calcium-dependent nitric oxide synthase causes ileitis and leukocytosis in guinea pigs. Dig Dis Sci. 1994 Jun;39(6):1185–1192. doi: 10.1007/BF02093782. [DOI] [PubMed] [Google Scholar]
  46. Miller M. J., Sadowska-Krowicka H., Chotinaruemol S., Kakkis J. L., Clark D. A. Amelioration of chronic ileitis by nitric oxide synthase inhibition. J Pharmacol Exp Ther. 1993 Jan;264(1):11–16. [PubMed] [Google Scholar]
  47. Miller M. J., Thompson J. H., Zhang X. J., Sadowska-Krowicka H., Kakkis J. L., Munshi U. K., Sandoval M., Rossi J. L., Eloby-Childress S., Beckman J. S. Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis. Gastroenterology. 1995 Nov;109(5):1475–1483. doi: 10.1016/0016-5085(95)90633-9. [DOI] [PubMed] [Google Scholar]
  48. Miller M. J., Zhang X. J., Barkemeyer B., Grisham M. B., Sadowska-Krowicka H., Eloby-Childress S., Clark D. A. Rabbit gut permeability in response to histamine chloramines and chemotactic peptide. Gastroenterology. 1992 Nov;103(5):1537–1546. doi: 10.1016/0016-5085(92)91175-4. [DOI] [PubMed] [Google Scholar]
  49. Miller M. J., Zhang X. J., Sadowska-Krowicka H., Chotinaruemol S., McIntyre J. A., Clark D. A., Bustamante S. A. Nitric oxide release in response to gut injury. Scand J Gastroenterol. 1993 Feb;28(2):149–154. doi: 10.3109/00365529309096062. [DOI] [PubMed] [Google Scholar]
  50. Minc-Golomb D., Tsarfaty I., Schwartz J. P. Expression of inducible nitric oxide synthase by neurones following exposure to endotoxin and cytokine. Br J Pharmacol. 1994 Jul;112(3):720–722. doi: 10.1111/j.1476-5381.1994.tb13136.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Nakane M., Schmidt H. H., Pollock J. S., Förstermann U., Murad F. Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett. 1993 Jan 25;316(2):175–180. doi: 10.1016/0014-5793(93)81210-q. [DOI] [PubMed] [Google Scholar]
  52. Natuzzi E. S., Ursell P. C., Harrison M., Buscher C., Riemer R. K. Nitric oxide synthase activity in the pregnant uterus decreases at parturition. Biochem Biophys Res Commun. 1993 Jul 15;194(1):1–8. doi: 10.1006/bbrc.1993.1776. [DOI] [PubMed] [Google Scholar]
  53. Nava E., Palmer R. M., Moncada S. Inhibition of nitric oxide synthesis in septic shock: how much is beneficial? Lancet. 1991 Dec 21;338(8782-8783):1555–1557. doi: 10.1016/0140-6736(91)92375-c. [DOI] [PubMed] [Google Scholar]
  54. Nguyen T., Brunson D., Crespi C. L., Penman B. W., Wishnok J. S., Tannenbaum S. R. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3030–3034. doi: 10.1073/pnas.89.7.3030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Nomura Y., Kitamura Y. Inducible nitric oxide synthase in glial cells. Neurosci Res. 1993 Nov;18(2):103–107. doi: 10.1016/0168-0102(93)90013-g. [DOI] [PubMed] [Google Scholar]
  56. Payne D., Kubes P. Nitric oxide donors reduce the rise in reperfusion-induced intestinal mucosal permeability. Am J Physiol. 1993 Jul;265(1 Pt 1):G189–G195. doi: 10.1152/ajpgi.1993.265.1.G189. [DOI] [PubMed] [Google Scholar]
  57. Pryor W. A., Lightsey J. W. Mechanisms of nitrogen dioxide reactions: initiation of lipid peroxidation and the production of nitrous Acid. Science. 1981 Oct 23;214(4519):435–437. doi: 10.1126/science.214.4519.435. [DOI] [PubMed] [Google Scholar]
  58. Rachmilewitz D., Karmeli F., Eliakim R., Stalnikowicz R., Ackerman Z., Amir G., Stamler J. S. Enhanced gastric nitric oxide synthase activity in duodenal ulcer patients. Gut. 1994 Oct;35(10):1394–1397. doi: 10.1136/gut.35.10.1394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Rachmilewitz D., Karmeli F., Okon E., Bursztyn M. Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity. Gut. 1995 Aug;37(2):247–255. doi: 10.1136/gut.37.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Rachmilewitz D., Karmeli F., Okon E. Sulfhydryl blocker-induced rat colonic inflammation is ameliorated by inhibition of nitric oxide synthase. Gastroenterology. 1995 Jul;109(1):98–106. doi: 10.1016/0016-5085(95)90273-2. [DOI] [PubMed] [Google Scholar]
  61. Rachmilewitz D., Stamler J. S., Karmeli F., Mullins M. E., Singel D. J., Loscalzo J., Xavier R. J., Podolsky D. K. Peroxynitrite-induced rat colitis--a new model of colonic inflammation. Gastroenterology. 1993 Dec;105(6):1681–1688. doi: 10.1016/0016-5085(93)91063-n. [DOI] [PubMed] [Google Scholar]
  62. Radi R., Beckman J. S., Bush K. M., Freeman B. A. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J Biol Chem. 1991 Mar 5;266(7):4244–4250. [PubMed] [Google Scholar]
  63. 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]
  64. Radi R., Rodriguez M., Castro L., Telleri R. Inhibition of mitochondrial electron transport by peroxynitrite. Arch Biochem Biophys. 1994 Jan;308(1):89–95. doi: 10.1006/abbi.1994.1013. [DOI] [PubMed] [Google Scholar]
  65. Ralston S. H., Todd D., Helfrich M., Benjamin N., Grabowski P. S. Human osteoblast-like cells produce nitric oxide and express inducible nitric oxide synthase. Endocrinology. 1994 Jul;135(1):330–336. doi: 10.1210/endo.135.1.7516867. [DOI] [PubMed] [Google Scholar]
  66. Ribbons K. A., Zhang X. J., Thompson J. H., Greenberg S. S., Moore W. M., Kornmeier C. M., Currie M. G., Lerche N., Blanchard J., Clark D. A. Potential role of nitric oxide in a model of chronic colitis in rhesus macaques. Gastroenterology. 1995 Mar;108(3):705–711. doi: 10.1016/0016-5085(95)90442-5. [DOI] [PubMed] [Google Scholar]
  67. Roediger W. E., Lawson M. J., Nance S. H., Radcliffe B. C. Detectable colonic nitrite levels in inflammatory bowel disease--mucosal or bacterial malfunction? Digestion. 1986;35(4):199–204. doi: 10.1159/000199368. [DOI] [PubMed] [Google Scholar]
  68. Rondouin G., Bockaert J., Lerner-Natoli M. L-nitroarginine, an inhibitor of NO synthase, dramatically worsens limbic epilepsy in rats. Neuroreport. 1993 Sep 3;4(10):1187–1190. [PubMed] [Google Scholar]
  69. Rubbo H., Denicola A., Radi R. Peroxynitrite inactivates thiol-containing enzymes of Trypanosoma cruzi energetic metabolism and inhibits cell respiration. Arch Biochem Biophys. 1994 Jan;308(1):96–102. doi: 10.1006/abbi.1994.1014. [DOI] [PubMed] [Google Scholar]
  70. Salzman A. L., Menconi M. J., Unno N., Ezzell R. M., Casey D. M., Gonzalez P. K., Fink M. P. Nitric oxide dilates tight junctions and depletes ATP in cultured Caco-2BBe intestinal epithelial monolayers. Am J Physiol. 1995 Feb;268(2 Pt 1):G361–G373. doi: 10.1152/ajpgi.1995.268.2.G361. [DOI] [PubMed] [Google Scholar]
  71. Sandoval M., Liu X., Oliver P. D., Zhang X. J., Clark D. A., Miller M. J. Nitric oxide induces apoptosis in a human colonic epithelial cell line, T84. Mediators Inflamm. 1995;4(4):248–250. doi: 10.1155/S0962935195000391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Seago N. D., Thompson J. H., Zhang X. J., Eloby-Childress S., Sadowska-Krowicka H., Rossi J. L., Currie M. G., Manning P. T., Clark D. A., Miller M. J. Inducible nitric oxide synthase and guinea-pig ileitis induced by adjuvant. Mediators Inflamm. 1995;4(1):19–24. doi: 10.1155/S0962935195000044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Stefanovic-Racic M., Meyers K., Meschter C., Coffey J. W., Hoffman R. A., Evans C. H. N-monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats. Arthritis Rheum. 1994 Jul;37(7):1062–1069. doi: 10.1002/art.1780370712. [DOI] [PubMed] [Google Scholar]
  74. Tepperman B. L., Brown J. F., Korolkiewicz R., Whittle B. J. Nitric oxide synthase activity, viability and cyclic GMP levels in rat colonic epithelial cells: effect of endotoxin challenge. J Pharmacol Exp Ther. 1994 Dec;271(3):1477–1482. [PubMed] [Google Scholar]
  75. Tepperman B. L., Brown J. F., Whittle B. J. Nitric oxide synthase induction and intestinal epithelial cell viability in rats. Am J Physiol. 1993 Aug;265(2 Pt 1):G214–G218. doi: 10.1152/ajpgi.1993.265.2.G214. [DOI] [PubMed] [Google Scholar]
  76. Tracey W. R., Nakane M., Kuk J., Budzik G., Klinghofer V., Harris R., Carter G. The nitric oxide synthase inhibitor, L-NG-monomethylarginine, reduces carrageenan-induced pleurisy in the rat. J Pharmacol Exp Ther. 1995 Jun;273(3):1295–1299. [PubMed] [Google Scholar]
  77. Vane J. R., Mitchell J. A., Appleton I., Tomlinson A., Bishop-Bailey D., Croxtall J., Willoughby D. A. Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2046–2050. doi: 10.1073/pnas.91.6.2046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Wallace J. L., Reuter B., Cicala C., McKnight W., Grisham M. B., Cirino G. Novel nonsteroidal anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat. Gastroenterology. 1994 Jul;107(1):173–179. doi: 10.1016/0016-5085(94)90074-4. [DOI] [PubMed] [Google Scholar]
  79. Weinberg J. B., Granger D. L., Pisetsky D. S., Seldin M. F., Misukonis M. A., Mason S. N., Pippen A. M., Ruiz P., Wood E. R., Gilkeson G. S. The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease: increased nitric oxide production and nitric oxide synthase expression in MRL-lpr/lpr mice, and reduction of spontaneous glomerulonephritis and arthritis by orally administered NG-monomethyl-L-arginine. J Exp Med. 1994 Feb 1;179(2):651–660. doi: 10.1084/jem.179.2.651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Wink D. A., Kasprzak K. S., Maragos C. M., Elespuru R. K., Misra M., Dunams T. M., Cebula T. A., Koch W. H., Andrews A. W., Allen J. S. DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science. 1991 Nov 15;254(5034):1001–1003. doi: 10.1126/science.1948068. [DOI] [PubMed] [Google Scholar]
  81. Worrall N. K., Lazenby W. D., Misko T. P., Lin T. S., Rodi C. P., Manning P. T., Tilton R. G., Williamson J. R., Ferguson T. B., Jr Modulation of in vivo alloreactivity by inhibition of inducible nitric oxide synthase. J Exp Med. 1995 Jan 1;181(1):63–70. doi: 10.1084/jem.181.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Yamada T., Sartor R. B., Marshall S., Specian R. D., Grisham M. B. Mucosal injury and inflammation in a model of chronic granulomatous colitis in rats. Gastroenterology. 1993 Mar;104(3):759–771. doi: 10.1016/0016-5085(93)91011-6. [DOI] [PubMed] [Google Scholar]
  83. 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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