Effect of nitric oxide on the colonic smooth muscle of patients with Hirschsprung's disease

Abstract

Hirschsprung's disease results in bowel obstruction because of a failure of smooth muscle relaxation in both the aganglionic segment of bowel and the internal anal sphincter (IAS). Nonadrenergic noncholinergic (NANC) nerves, which use nitric oxide (NO) as their chemical messenger, are responsible for relaxing smooth muscle in normal bowel and the IAS. Previous work indicates that the cause of the aganglionic colon's inability to relax may be a lack of NANC nerves. To test this hypothesis, the authors compared the effect of an exogenous source of NO, S-nitroso-N-acetylpenicillamine (SNAP), on the isometric tension of smooth muscle strips taken from the ganglionic colon, aganglionic colon, and IAS of patients with Hirschsprung's disease. Exposure of ganglionic and aganglionic colon specimens to SNAP (10 −3 to 10 −5 mol/L) resulted in up to 70% reduction of resting tension. This relaxation occurred in a dose-dependent fashion and could be promptly reversed by the addition of the NO antagonist methylene blue. However, SNAP had no demonstrable effect on the smooth muscle strips taken from the IAS of patients with Hirschsprung's disease. This finding suggests that, in the aganglionic colon, a deficiency of NANC nerves contributes to the development of bowel obstruction. However, the failure of the IAS to relax in Hirschsprung's disease appears to be unrelated to NO and the NANC nervous system.