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.
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REFERENCES
Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142, 1991
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
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
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
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
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
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
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
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
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
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
Calver A, Coller J, Vallance P: Nitric oxide and cardiovascular control. Exp Physiol 78:303–326, 1993
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
Ignarro LJ: Signal transduction mechanism involving nitric oxide. Biochem Pharmacol 41:485–490, 1991
Synder SH, Bredt DS: Nitric oxide as a neuronal messenger. TIPS 12:125–128, 1991
Synder SH: Nitric oxide: First in a new class of neurotransmitters? Science 257:494–496, 1992
Sanders KM, Ward SM: Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol 262:G379–G392, 1992
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
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
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
Rachmilewitz D, Stamler JS, Karmeli F: Peroxynitrite-induced rat colitis—a new model of colonic inflammation. Gastroenterology 105:1681–1688, 1993
Rachmilewitz D, Karmeli F, Okon E, Bursztyn M: Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity. Gut 36:247–255, 1995
Boughton-Smith NK, Evans SM, Hawkey CJ: Nitric oxide synthase activity in ulcerative colitis and Crohn's disease. Lancet 342:338–340, 1993
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
Reynolds PD, Middleton SJ, Hunter P: High expression of iNOS in colonic mucosa in ulcerative colitis. Gut 36:A56, 1995
Lundberg JON, Hellstrom PM, Lundberg JM, Alving K: Greatly increase luminal nitric oxide in ulcerative colitis. Lancet 344:1673–1674, 1994
Middleton SJ, Shorthouse M, Hunter JO: Increased nitric oxide synthesis in ulcerative colitis. Lancet 341:465–466, 1993
Trann DD, Visser JJ, Pool MO: Enhanced systemic nitric oxide production in inflammatory bowel disease. Lancet 341:1150, 1993
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
Boughton-Smith NK: Pathological and therapeutic implication for nitric oxide in inflammatory bowel disease. J R Soc Med 87:312–313, 1994
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
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
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
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
Leunberger UR, Gauch R, Baumgartner E: Determination of nitrate and bromide in foodstuff by HPLC. J Chromatogr 202:461–465, 1980
Corti F, Hua L, Passaro A: NO release from nitrocompounds investigated by spectrophotometric and HPLC analysis. Pharmacol Res 26(1):247, 1992
Bredt DS, Snyder SH: Isolation of nitric oxide synthase, a calmomodulin requiring enzyme. Proc Natl Acad Sci USA 87:682–685, 1990
Bradford MM: A rapid and sensitive method for the quantification of protein dye binding. Anal Biochem 72:248–254, 1976
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
Roediger WEW, Lawson MJ, Radcliffe BC: Nitrite from inflammatory cells—a cancer risk factor in ulcerative colitis? Dis Colon Rectum 33:1034–1036, 1990
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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
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DOI: https://doi.org/10.1023/A:1018897519880