Nitric oxide synthase distribution in the enteric nervous system of Hirschsprung's disease

Background: Hirschsprung's disease is characterized histologically by aganglionosis and functionally by impaired relaxation of the gut. Nitric oxide has recently been described pharmacologically as a major inhibitory mediator in the gut musculature in laboratory animals. The present study hypothesized that NO could be involved in motility disorders of the human gut. The aim was to study the neuronal enzyme synthetizing NO in the ganglionic and aganglionic human gut. Methods: Reduced nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry and immunohistochemistry with a specific polyclonal antiserum were used to examine NO synthase distribution in the enteric nervous system in six patients with Hirschsprung's disease and five control patients. Results: NO synthase was selectively absent in the plexus area and in the musculature of the aganglionic segments, whereas moderate staining was observed in the hypertrophied nerve bundles in the submucosa. In contrast, in the ganglionic segment NO synthase was abundantly present, in a pattern similar to that of the normal colon. Conclusions: These findings suggest the involvement of NO in the physiopathology of Hirschsprung's disease.