DISTRIBUTION OF NITRIC-OXIDE SYNTHASE CONTAINING NEURONS IN THE RECTAL MYENTERIC PLEXUS AND ANAL-CANAL - MORPHOLOGIC EVIDENCE THAT NITRIC-OXIDE MEDIATES THE RECTOANAL INHIBITORY REFLEX

PURPOSE: Following the demonstration that a novel neurotransmitter, nitric oxide (NO), is released during neurogenic relaxation of the internal anal sphincter in vitro, it has been suggested that NO could mediate the rectoanal inhibitory reflex in vivo. The aim of this study was to establish whether the distribution of NO-producing nerves in the anorectum is consistent with this proposed role. METHODS: NO is synthesized in neurons which contain the enzyme nitric oxide synthase and their presence in the anorectum was determined in tissue obtained from nine abdominoperineal and three anterior resection specimens in patients undergoing surgery for rectal carcinoma. Cryostat sections were stained for nitric oxide synthase immunoreactivity, pan-neuronal/axonal immunoreactivity, and NADPH diaphorase activity. RESULTS: Nitric oxide synthase immunoreactivity is present in a subpopulation of neurons in rectal myenteric ganglia which also contain NADPH diaphorase activity. Use of the latter histochemical technique enabled the structure and distribution of nitric oxide synthase containing neurons to be determined in whole-mount preparations. Individual neurons have Dogiel type 1 morphology and are present throughout the rectal myenteric plexus. In the distal rectum, positively stained axons enter shunt fascicles which descend into the anal canal, where they ramify into and throughout the internal anal sphincter. Within the sphincter, positively stained nerves lie in close proximity to smooth muscle cells. CONCLUSION: These results are consistent with the hypothesis that NO is the neurotransmitter that mediates the rectonal inhibitory reflex.