ROLE OF NITRIC-OXIDE IN RELAXATION OF THE LONGITUDINAL LAYER OF RECTAL SMOOTH-MUSCLE

PURPOSE: This study was designed to investigate the role of nitric oxi de in neurogenic relaxation of the longitudinal layer of human rectal smooth muscle. METHODS: Tissue was obtained from the mid rectum of pat ients undergoing anterior resection for carcinoma. Adjacent strips of longitudinal muscle were dissected and mounted in organ baths for isom etric tension recording. In preliminary experiments to determine the r esponse of strips to cholinergic, adrenergic, and potential excitatory agonists, strips were superfused with standard Krebs solution (37 +/- 0.5 degrees C; pH, 7.4 +/- 0.05). Investigation of inhibitory, nonadr energic noncholinergic responses required the addition of 3 x 10(-6) M histamine to induce reproducible and stable tension for five-minute ' 'test'' periods, during which electrical field stimulation (EFS) and a dditional drugs were applied. In these experiments, strips were superf used with Krebs solution that contained atropine sulfate (3 x 10(-6) M ) and guanethidine (3 x 10(-6) M). RESULTS: The response to cholinergi c and adrenergic agonists was typical of nonsphincter specialized gast rointestinal smooth muscle. EFS elicited frequency-dependent, neurogen ic (tetrodotoxin-sensitive) relaxations of precontracted strips, which were reduced in dose-dependent fashion by addition of Nw-nitro-L-argi nine and restored by addition of 3 X 10(-4) M L-arginine but not by D- arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mi micked the relaxant response induced by EFS. CONCLUSION: Smooth muscle from the longitudinal layer of human rectum receives an intrinsic inh ibitory innervation mediated by nitric oxide.