PURPOSE: The pathophysiology of Chagas' disease is incompletely understood. Neuronal nitric oxide has been cited as a candidate neurotransmitter responsible for relaxation of the internal anal sphincter. Neuronal nicotinamide adenine dinucleotide phosphate diaphorase can be used as a marker for neuronal nitric oxide synthase. This study was designed to examine the alterations of the nitric oxidecontaining neurons in the enteric nervous system of the colon of patients who underwent resections for advanced megacolon and to compare these specimens with small-bowel specimens from the same patients and with specimens from control subjects. METHODS: Specimens from resected rectum and extramucosal small-bowel biopsy specimens from 11 patients with Chagas megacolon but no apparent small-bowel clinical involvement were compared with the uninvolved colon and jejunum of 10 control patients with colon cancer. Tissues were fixed in Zamboni solution and evaluated by histochemistry for nicotinamide adenine dinucleotide phosphate diaphorase-containing neurons. Reactivity was evaluated on a 0 to 4 scale in the longitudinal muscle, myenteric plexus, circular muscle, submucosal plexus, and mucosa. RESULTS: Specimens from control patients showed well-stained myenteric and submucosal neurons and an abundant network of terminal nerve fibers in the muscle layers. Chagasic specimens had decreased staining in all layers of the gut. Overall there was a statistically significant decrease in nicotinamide adenine dinucleotide phosphate diaphorase-containing neurons. Biopsy specimens from clinically uninvolved small bowel of patients with Chagas' disease also showed decreased reactivity, but to a lesser degree. CONCLUSIONS: Nicotinamide adenine dinucleotide phosphate diaphorase activity is decreased in patients with advanced megacolon. The alterations are more relevant in the myenteric plexus and the circular muscle. Reactivity is also diminished in the clinically uninvolved small bowel, but to a lesser extent.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Okumura M, Corrêa-Neto A. Produçõ experimental de megas em animais inoculados comTrypanosoma cruzi. Rev Hosp Cl'n Fac Med São Paulo 1961;18:5.
Koberle F. Chagas' disease and Chagas' syndrome. The pathology of American trypanosomiasis. Adv Parasitol 1968;6:63–116.
Habr-Gama A, Raia A, Corrêa Neto A. Motility of the sigmoid colon and rectum: contribution to the physiopathology of megacolon in Chagas' disease. Dis Colon Rectum 1971;14:291–304.
Burleigh DE, D'Mello A, Parks AG. Responses of isolated human internal anal sphincter to drugs and electrical field stimulation. Gastroenterology 1979;77:484–90.
Burleigh DE. Non-adrenergic non-cholinergic inhibitory neurons in the human internal anal sphincter muscle. J Pharm Pharmacol 1983;35:258–60.
Gillespie JS, Xiu X, Martin W. The effects ofL-arginine andN G-monomethylL-arginine on the response of the rat anococcygeus muscle to NANC nerve stimulation. Br J Pharmacol 1989;98:1080–2.
Li GG, Rand MJ. Evidence for a role of nitric oxide in the neurotransmitter system mediating relaxation of the rat anococcygeus muscle. Clin Exp Pharmacol Physiol 1989;16:933–8.
Bult H, Boeckxstaens GE, Pelckmans PA, Jordaens FH, Van Maercke YM, Herman AG. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature 1990;345:346–7.
Sanders KM, Ward SM. Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am J Physiol 1992;262:G3:79–92.
Keef KD, Du C, Ward SM, McGregor B, Sanders KM. Enteric inhibitory neural regulation of human colonic muscle: the role of nitric oxide. Gastroenterology 1993;105:1009–16.
Stebbing JF, Brading AF, Mortensen NJ. Nitrergic innervation and relaxant response of rectal circular smooth muscle. Dis Colon Rectum 1996;39:294–9.
Bredt DS, Hwang PM, Snyder SH. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 1990;347:768–70.
Costa M, Furness JB, Pompolo S,et al. Projections and chemical coding of neurons with immunoreactivity for nitric oxide synthase in the guinea-pig small intestine. Neurosci Lett 1992;148:121–5.
Young HM, Furness JB, Shuttleworth CW, Bredt DS, Snyder SH. Co-localization of nitric oxide synthase immunoreactivity and NADPH diaphorase staining in neurons of the guinea pig intestine. Histochemistry 1992;97:375–8.
Ward S, Xue C, Shuttleworth CW, Bredt DS, Snyder SH, Sanders KM. NADPH diaphorase and nitric oxide synthase co-localization in enteric nerves of the canine proximal colon. Am J Physiol 1992;263:G2:77–84.
Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH. Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 1991;88:7797–801.
Hope BT, Michael GJ, Knigge KM, Vincent SR. Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci USA 1991;88:2811–4.
O'Kelly T, Brading A, Mortensen N. Nerve mediated relaxation of the human internal sphincter: the role of nitric oxide. Gut 1993;34:689–93.
Bealer JF, Natuzzi ES, Buscher C,et al. Nitric oxide synthase is deficient in the aganglionic colon of patients with Hirschsprung's disease. Pediatrics 1994;93:647–51.
Moore BG, Singaram C, Eckhoff DE, Gaumnitz EA, Starling JR. Immunohistochemical evaluation of ultrashort-segment Hirschsprung's disease: report of three cases. Dis Colon Rectum 1996;39:817–22.
Cuffari C, Rubin SZ, Krantis A. Routine use of the nitric oxide stain in the differential diagnosis of Hirschsprung's disease. J Pediatr Surg 1993;28:1202–4.
Vanderwinden JM, De Laet MH, Schiffmann SN,et al. Nitric oxide synthase distribution in the enteric nervous system of Hirschsprung's disease. Gastroenterology 1993;105:969–73.
O'Kelly TJ, Brading AF, Mortensen NJ. Nerve mediated relaxation of the human internal anal sphincter: the role of nitric oxide. Gut 1993;34:689–93.
Gustafsson BI, Delbro DS. Tonic inhibition of small intestinal motility by nitric oxide. J Auton Nerv Syst 1993;44:179–87.
Middleton SJ, Cuthbert AW, Shorthouse M, Hunter JO. Nitric oxide affects mammalian distal colonic muscle by tonic neural inhibition. Br J Pharmacol 1993;108:974–9.
Rattan S, Sarkar A, Chadker S. Nitric oxide pathway in rectoanal inhibitory reflex of opossum internal anal sphincter. Gastroenterology 1992;103:43–50.
O'Kelly TJ, Davies JR, Brading AF, Mortensen NJ. Distribution of nitric oxide synthase containing neurons in the rectal myenteric plexus and canal anal: morphologic evidence that nitric oxide mediates the rectoanal inhibitory reflex. Dis Colon Rectum 1994;37:350–7.
Loder PB, Kamm MA, Nicholls RJ, Phillips RK. Reversible chemical sphincterotomy by local application of glyceryl trinitrate. Br J Surg 1994;81:1386–9.
Lund JN, Sholefield JH. A randomised, prospective, double-bind, placebo-controlled trial of glyceryl trinitrate ointment in treatment of anal fissure. Lancet 1997;349:11–4.
Schouten WR, Briel JW, Boerma MO, Auwerda JJ, Wilms EB, Graatsma BH. Pathophysiological aspects and clinical outcome of intra-anal application of isosorbide dinitrate in patients with chronic anal fissure. Gut 1996;39:465–9.
Read at the meeting of the Society for Surgery of the Alimentary Tract, Washington, D.C., May 10 to 15, 1997.
About this article
Cite this article
Ribeiro, U., Safatle-Ribeiro, A.V., Habr-Gama, A. et al. Effect of chagas' disease on nitric oxide-containing neurons in severely affected and unaffected intestine. Dis Colon Rectum 41, 1411–1417 (1998). https://doi.org/10.1007/BF02237058
- Chagas' disease
- Nitric oxide synthase neurons
- Neuronal nicotinamide adenine dinucleotide phosphate diaphorase