The role of nitrergic system on the contractility of colonic circular smooth muscle in Hirschsprung's disease.

The contribution of nitrergic tone on the contractility of colonic smooth muscle in Hirschsprung's disease (HD) was investigated.

Methods: Ganglionic and aganglionic bowel specimens were taken from 8 patients with HD during pull-through operations and electrical field stimulation (EFS)-induced isometric contractions of the circular smooth muscle were recorded in vitro. Isolated circular muscle strips prepared from colonic segments of sex- and age-matched patients (n = 3) who underwent surgery for nonmotility-related colonic diseases formed the control group. Statistical analysis was performed by two way analysis of variance and unpaired Student's ttest.

Results: The amplitude of spontaneous rhythmic activity was lower in aganglionic segments than in ganglionic ones. The amplitudes of contractile responses were significantly greater in aganglionic segments. In ganglionic preparations, N(omega)-nitro-L-arginine (L-NNA) addition into the medium increased the contractile responses to the level of aganglionic preparations. This increase was completely blocked by L-arginine application. Neither L-NNA nor L-arginine produced any change in aganglionic segments. A relaxation phase was detected in both ganglionic and aganglionic segments. In ganglionic preparations, this relaxation phase was completely inhibited by L-NNA and restored by L-arginine, whereas no effect was detected in aganglionic ones. Responses obtained from the control group were similar to the ganglionic segments of HD patients.

Conclusions: In normal colon and as well as in ganglionic segments of HD, the evoked contractile activity and relaxations are under the tonic influence of the nitrergic system. Aganglionic segments totally lack the nitrergic activity in both evoked contraction and relaxation responses, while still maintaining an inefficient relaxation capacity under unknown mechanisms.