Skip to main content
Log in

Intracolonic Release of Nitric Oxide During Trinitrobenzene Sulfonic Acid Rat Colitis

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Nitric oxide is thought to play an importantrole in modulating the inflammatory process. Recently anincrease in the inducible form of nitric oxide synthase(iNOS) has been found in the rat trinitrobenzene sulfonic acid model of experimental colitis,and inhibition of nitric oxide synthase activityresulted in an amelioration of tissue injury. The aim ofour study was to evaluate in vivo intracolonic release of nitric oxide in this model of colitis.Experimental colitis was induced in male Sprague-Dawleyrats by a single intracolonic administration oftrinitrobenzene sulfonic acid. Nitrite levels weredetermined in rectal dialysates by HPLC. The tissuemyeloperoxidase and iNOS and the luminal leukotrieneB4 were also measured. Nitrite levels weresignificantly increased in rectal dialysates duringcolitis and correlated significantly with tissue myeloperoxidase andiNOS activity. The correlation between nitrite dialysatelevels and wall iNOS activity confirms that nitrite indialysates is produced by inflammatory cells and not by colonic bacterial flora.Determination of nitrite levels in rectal dialysatesseems a valuable method to monitor colonic inflammationin rat trinitrobenzene sulfonic acid colitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142, 1991

    Google Scholar 

  2. Stuehr DJ, Marlietta MA: Mammalian nitrate biosynthesis: Mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc Natl Acad Sci USA 82:7738, 1985

    Google Scholar 

  3. Bredt DS, Hwang PM, Glatt CE, Lowestein C, Reed RR, Snyder SH: Cloned and expressed nitric oxide synthase structurally resemble cytochrome P450 reductase. Nature 351:714–718, 1991

    Google Scholar 

  4. Nakane M, Schmidt HHHW, Pollock JS, Forstermann U, Murad F: Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett 316:175–180, 1993

    Google Scholar 

  5. Lamas S, Marsden PA, Li GK, Tempst P, Michel T: Endothelial nitric oxide synthase: Molecular cloning and characterization of distinct constitutive enzyme isoform. Proc Natl Acad Sci USA 89:6348–6352, 1992

    Google Scholar 

  6. Xie Q, Cho HJ, Calaycay J, Mumford RA, Swiderek KM, Lee TD, Ding A, Troso T, Nathan C: Cloning and characte rization of inducible nitric oxide synthase from mouse macrophages. Science 256:225–228, 1992

    Google Scholar 

  7. McCall TB, Boughton Smith NK, Palmer MJ, Whittle BJR, Moncada A: Synthesis of nitric oxide from L-arginine by neutrophils. Release and interaction with superoxide anion. Biochem J 261:295–296, 1989

    Google Scholar 

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

    Google Scholar 

  9. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA: Apparent hydroxyl radical production by peroxynitrite: implications for endothelial cell injury from nitric oxide. Proc Natl Acad Sci USA 87:1620–1624, 1990

    Google Scholar 

  10. Nussler AK, Di Silvio M, Billiar TR, Hoffman RA, Geller DA, Selby R, Madariaga J, Simmons RL: Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokine and endotoxin. J Exp Med 176:261–264, 1992

    Google Scholar 

  11. Nunokawa Y, Ishida N, Tanaka S: Cloning of inducible nitric oxide synthase in rat vascular smooth muscle cells. Biochem Biophys Res Commun 181:89–94, 1993

    Google Scholar 

  12. Calver A, Coller J, Vallance P: Nitric oxide and cardiovascular control. Exp Physiol 78:303–326, 1993

    Google Scholar 

  13. Sessa WC, Barber CM, Lynch KR: Mutation of N-myristoylation site converts endothelial cell nitric oxide synthase from a membrane to a cytostic protein. Circ Res 72:921–924, 1993

    Google Scholar 

  14. Ignarro LJ: Signal transduction mechanism involving nitric oxide. Biochem Pharmacol 41:485–490, 1991

    Google Scholar 

  15. Synder SH, Bredt DS: Nitric oxide as a neuronal messenger. TIPS 12:125–128, 1991

    Google Scholar 

  16. Synder SH: Nitric oxide: First in a new class of neurotransmitters? Science 257:494–496, 1992

    Google Scholar 

  17. Sanders KM, Ward SM: Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol 262:G379–G392, 1992

    Google Scholar 

  18. Boughton NK, Evans SM, Laszio F, Whittle BJR, Moncada S: The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat. Br J Pharmacol 110:1189–1195, 1993

    Google Scholar 

  19. Boughton Smith NK, Evans SM, Whittle BRJ: Characterization of nitric oxide synthase activity in the rat colonic mucosa and muscle after endotoxin and in a model of colitis. Agents Actions 41:223–225, 1994

    Google Scholar 

  20. Miller MJS, Sadowska-Krowicka A, Chontinaruemol S, Kakkis JL, Clarke DA: Amelioration of chronic ileitis by nitric oxide synthase inhibition. J Pharmacol Exp Ther 264:11–16, 1993

    Google Scholar 

  21. Rachmilewitz D, Stamler JS, Karmeli F: Peroxynitrite-induced rat colitis—a new model of colonic inflammation. Gastroenterology 105:1681–1688, 1993

    Google Scholar 

  22. Rachmilewitz D, Karmeli F, Okon E, Bursztyn M: Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity. Gut 36:247–255, 1995

    Google Scholar 

  23. Boughton-Smith NK, Evans SM, Hawkey CJ: Nitric oxide synthase activity in ulcerative colitis and Crohn's disease. Lancet 342:338–340, 1993

    Google Scholar 

  24. Mourelle M, Caellas F, Guarner F, Malagelada JR: Toxic megacolon in patients with chronic ulcerative colitis may be due to induction of nitric oxide synthase. Gastroenterology 104:A749, 1993

    Google Scholar 

  25. Reynolds PD, Middleton SJ, Hunter P: High expression of iNOS in colonic mucosa in ulcerative colitis. Gut 36:A56, 1995

    Google Scholar 

  26. Lundberg JON, Hellstrom PM, Lundberg JM, Alving K: Greatly increase luminal nitric oxide in ulcerative colitis. Lancet 344:1673–1674, 1994

    Google Scholar 

  27. Middleton SJ, Shorthouse M, Hunter JO: Increased nitric oxide synthesis in ulcerative colitis. Lancet 341:465–466, 1993

    Google Scholar 

  28. Trann DD, Visser JJ, Pool MO: Enhanced systemic nitric oxide production in inflammatory bowel disease. Lancet 341:1150, 1993

    Google Scholar 

  29. Rachmilewitz D, Stamler JS, Bachwich D, Karmeli F, Acxerman Z, Podolsky DK: Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease. Gut 36:718–723, 1995

    Google Scholar 

  30. Boughton-Smith NK: Pathological and therapeutic implication for nitric oxide in inflammatory bowel disease. J R Soc Med 87:312–313, 1994

    Google Scholar 

  31. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL: Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803, 1989

    Google Scholar 

  32. Vilaseca J, Salas A, Guarner F, Rodrigues R and Malagelada JR: Participation of thromboxane and other eicosanoids synthesis in the course of experimental inflammatory colitis. Gastroenterology 98:269–277, 1990

    Google Scholar 

  33. Lauritsen K, Hansen J, Bytzer P: Effects of sulphasalazine and disodium-azodisalicylate on colonic PGE2 concentration determined by equilibrium in vivo dialysis of faeces in patients with ulcerative colitis and healthy controls. Gut 25:1271–1278, 1984

    Google Scholar 

  34. Bradley PP, Priebat DA, Christensen RD: Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209, 1982

    Google Scholar 

  35. Leunberger UR, Gauch R, Baumgartner E: Determination of nitrate and bromide in foodstuff by HPLC. J Chromatogr 202:461–465, 1980

    Google Scholar 

  36. Corti F, Hua L, Passaro A: NO release from nitrocompounds investigated by spectrophotometric and HPLC analysis. Pharmacol Res 26(1):247, 1992

    Google Scholar 

  37. Bredt DS, Snyder SH: Isolation of nitric oxide synthase, a calmomodulin requiring enzyme. Proc Natl Acad Sci USA 87:682–685, 1990

    Google Scholar 

  38. Bradford MM: A rapid and sensitive method for the quantification of protein dye binding. Anal Biochem 72:248–254, 1976

    Google Scholar 

  39. Wallace JL, McNaughton WK, Morris GP, Beck PL: Inhibition of leukotriene synthesis markedly accelerates healing in a rat model of inflammatory bowel disease. Gastroenterology 96:29–36, 1989

    Google Scholar 

  40. Roediger WEW, Lawson MJ, Radcliffe BC: Nitrite from inflammatory cells—a cancer risk factor in ulcerative colitis? Dis Colon Rectum 33:1034–1036, 1990

    Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferretti, M., Gionchetti, P., Rizzello, F. et al. Intracolonic Release of Nitric Oxide During Trinitrobenzene Sulfonic Acid Rat Colitis. Dig Dis Sci 42, 2606–2611 (1997). https://doi.org/10.1023/A:1018897519880

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018897519880

Navigation