The inhibitory role of nitric oxide in the control of porcine and human sphincter of Oddi activity

Background—The possible role of nitric oxide inthe regulation of the sphincter of Oddi is not known in species with aresistor-like sphincter of Oddi such as humans and pigs.
Methods—Sphincter of Oddi perfusion manometry andsimultaneous electromyography (EMG) were recorded transduodenally ineight anaesthetised pigs. Acetylcholine (4 µg/kg) was givenintra-arterially, with or without sodium nitroprusside(10-100 µg/kg), an exogenous nitric oxide donor. For in vitrostudies the sphincter was removed from the eight pigs and from sixpatients undergoing pancreaticoduodenectomy, cut into rings, and theamplitude of contraction was measured in an ex vivo bath. Each ring wasstimulated with acetylcholine (100 µM) and KCl (125 mM). Thestimulation was repeated after incubation with L-NAME (astereospecific competitive inhibitor of nitric oxide synthase), withL-NAME plus L-arginine (a substrate for nitricoxide synthase), and with sodium nitroprusside. The sphincter ringswere then submersed in liquid nitrogen and stored. Immunohistochemicalanalysis was used to localise nitric oxide synthase in the pig andhuman sphincter specimens.
Results—In vivo EMG revealed 2-3 phasic burstsper minute with the basal pressure variation 6-40 mm Hg.Acetylcholine induced a large electrical burst and the pressureincreased by (mean (SE)) 20 (10) mm Hg (p <0.01) for 17 (4) seconds.After sodium nitroprusside (10 µg/kg) acetylcholine did not inducepressure changes and electrical activity was almost abolished. Invitro, L-NAME increased the KCl induced sphinctercontraction in both pig and human specimens (p<0.01). In human, butnot in pig, specimens L-NAME increased the amplitude ofacetylcholine induced contraction (p<0.01). L-Arginine partly reversed the effect of L-NAME in both pig and humanspecimens. Sodium nitroprusside decreased the acetylcholine and KClinduced contractions in both pig and human specimens.Immunohistochemical studies localised nitric oxide synthase to richplexi of nerve fibres in the mucosa and the muscle in both pig andhuman sphincter of Oddi.
Conclusions—The sphincter of Oddi in both pigs andhumans has endogenous nitric oxide synthase activity andimmunoreactivity. Inhibition of endogenous nitric oxide productionenhances contractility while exogenous nitric oxide decreasessphincter contractility and electrical activity.

Keywords:NO; nitric oxide synthase; nitroprusside; sphincterof Oddi; pig; human