Role of nitric oxide in relaxation of the longitudinal layer of rectal smooth muscle.

Abstract

This study was designed to investigate the role of nitric oxide in neurogenic relaxation of the longitudinal layer of human rectal smooth muscle. Tissue was obtained from the mid rectum of patients undergoing anterior resection for carcinoma. Adjacent strips of longitudinal muscle were dissected and mounted in organ baths for isometric tension recording. In preliminary experiments to determine the response 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, nonadrenergic 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 additional drugs were applied. In these experiments, strips were superfused with Krebs solution that contained atropine sulfate (3 x 10(-6) M) and guanethidine (3 x 10(-6) M). The response to cholinergic and adrenergic agonists was typical of nonsphincter specialized gastrointestinal smooth muscle. EFS elicited frequency-dependent, neurogenic (tetrodotoxin-sensitive) relaxations of precontracted strips, which were reduced in dose-dependent fashion by addition of N omega-nitro-L-arginine and restored by addition of 3 x 10(-4) M L-arginine but not by D-arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mimicked the relaxant response induced by EFS. Smooth muscle from the longitudinal layer of human rectum receives an intrinsic inhibitory innervation mediated by nitric oxide.