NITRERGIC INNERVATION AND RELAXANT RESPONSE OF RECTAL CIRCULAR SMOOTH-MUSCLE

PURPOSE: This study was designed to investigate whether nitric oxide m ediates inhibitory innervation in human rectal circular smooth muscle. METHODS: Tissue was obtained from the midrectum of patients undergoin g anterior resection for carcinoma. Adjacent strips of circular muscle were dissected and mounted in superfusion organ baths for isometric t ension recording and initially loaded with 1 g of weight. Strips were continuously bathed with standard Krebs solution (37 degrees C, bubble d with 97 percent O-2/3 percent CO2) containing 3 x 10(-6) M guanethid ine and 3 x 10(-6) M atropine sulfate to block adrenergic and muscarin ic cholinergic neurotransmission. After equilibration, strips had no i ntrinsic tone, and reproducible and stable tension was, therefore, ind uced by the addition of 3 x 10(-6) M histamine for five-minute ''test' ' periods, during which electrical field stimulation (EFS) and additio nal drugs were applied. RESULTS: EFS elicited frequency-dependent, neu rogenic (tetrodotoxin-sensitive) relaxations of precontracted strips. Addition of N-omega-nitro-L-arginine, a powerful competitive inhibitor of nitric oxide synthase, reduced the relaxant response to EFS in a d ose-dependent fashion, an effect reversed 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. C ONCLUSIONS: Human rectal circular smooth muscle receives an intrinsic inhibitory innervation mediated by nitric oxide. The presence of a res idual response following blockade of the enzyme nitric oxide synthase suggests the involvement of additional neurotransmitters.