THE INHIBITORY ROLE OF NITRIC-OXIDE IN THE CONTROL OF PORCINE AND HUMAN SPHINCTER OF ODDI ACTIVITY

Background-The possible role of nitric oxide in the regulation of the sphincter of Oddi is not known in species with a resistor-like sphinct er of Oddi such as humans and pigs. Methods-Sphincter of Oddi perfusio n manometry and simultaneous electromyography (EMG) were recorded tran sduodenally in eight anaesthetised pigs. Acetylcholine (4 mu g/kg) was given intraarterially, with or without sodium nitroprusside (10-100 m u g/kg), an exogenous nitric oxide donor. For in vitro studies the sph incter was removed from the eight pigs and from six patients undergoin g pancreaticoduodenectomy, cut into rings, and the amplitude of contra ction was measured in an ex vivo bath. Each ring was stimulated with a cetylcholine (100 mu M) and KCI (125 mM). The stimulation was repeated after incubation with L-NAME (a stereospecific competitive inhibitor of nitric oxide synthase), with L-NAME plus L-arginine (a substrate fo r nitric oxide synthase), and with sodium nitroprusside. The sphincter rings were then submersed in liquid nitrogen and stored. Immunohistoc hemical analysis was used to localise nitric oxide synthase in the pig and human sphincter specimens. Results-In vivo EMG revealed 2-3 phasi c bursts per minute with the basal pressure variation 6-40 mm Hg. Acet y]choline induced a large electrical burst and the pressure increased by (mean (SE)) 20 (10) mm Hg (p <0.01) for 17 (4) seconds. After sodiu m nitroprusside (10 mu g/kg) acetylcholine did not induce pressure cha nges and electrical activity was almost abolished. In vitro, L-NAME in creased the KCl induced sphincter contraction in both pig and human sp ecimens (p<0.01). In human, but not in pig, specimens L-NAME increased the amplitude of acetylcholine induced contraction (p<0.01). L-Argini ne partly reversed the effect of L-NAME in both pig and human specimen s. Sodium nitroprusside decreased the acetylcholine and KCI induced co ntractions in both pig and human specimens. Immunohistochemical studie s localised nitric oxide synthase to rich plexi of nerve fibres in the mucosa and the muscle in both pig and human sphincter of Oddi. Conclu sions-The sphincter of Oddi in both pigs and humans has endogenous nit ric oxide synthase activity and immunoreactivity. Inhibition of endoge nous nitric oxide production enhances contractility while exogenous ni tric oxide decreases sphincter contractility and electrical activity.