DISTRIBUTION OF NITRIC-OXIDE SYNTHASE-CONTAINING NERVES IN THE AGANGLIONIC INTESTINE OF MUTANT RATS - A HISTOCHEMICAL-STUDY

We examined the distribution of nerves containing nitric oxide synthas e in the intestine of congenitally aganglionic rats, using a reduced n icotinamide adenine dinucleotide phosphate diaphorase histochemical me thod for whole-mount and cryostat specimens. A constricted intestinal segment extends from the terminal ileum to the anus in this mutant. No nerve elements with the activity were found in the affected terminal ileum, cecum, and proximal colon. Although intrinsic ganglionic neuron s were absent along the constricted intestine, nerve fibers with the a ctivity were found in both the submucous and intermuscular layers dist al to the proximal colon. These fibers increased in density towards th e rectum, forming hypertrophic nerve bundles and unusual fiber network s. However, positive fibers were never seen within the circular and lo ngitudinal musculature of the constricted lesion. Some of these hypert rophic nerve bundles were continuous with ectopic ganglia that were si tuated in the adventitial connective tissue around the lower rectum an d in the submucosa near the anus. The hypertrophic nerve bundles seeme d to have an extrinsic origin; some of them may have originated from e ctopic ganglia. These results suggest that the defective distribution of nerves containing nitric oxide synthase may be involved in the path ogenesis of congenital colonic aganglionosis.