Involvement of the L-arginine-nitric oxide pathway in internal anal sphincter relaxation.

The purpose of this study was to examine the role of the L-arginine-nitric oxide pathway in neurogenic relaxation of the internal anal sphincter. Muscle strips representing the internal anal sphincter were prepared from 17 adult opossums. The preparations were mounted in organ baths for recording of isometric tension. N omega-nitro-L-arginine, an agent known to inhibit the L-arginine-nitric oxide pathway, concentration-dependently reduced relaxations induced by transmural field stimulation. At the highest concentration of N omega-nitro-L-arginine (10(-4) mol/L), no relaxation was evoked at any frequency tested (0.5-40 Hz). The inhibitory response to exogenous vasoactive intestinal polypeptide was unaffected by N omega-nitro-L-arginine pretreatment, indicating that vasoactive intestinal polypeptide relaxation does not use the L-arginine-nitric oxide pathway. In addition, responses to forskolin and sodium nitroprusside were not influenced by N omega-nitro-L-arginine preincubation, suggesting that the effect observed was not caused by a direct influence on the adenylate or the guanylate cyclases. It is concluded that the nonadrenergic, noncholinergic innervation of the internal anal sphincter involves an inhibitory substance generated from the L-arginine-nitric oxide pathway. Whether this substance is nitric oxide or a related nitroso compound remains to be settled.