Nitric oxide inhibits resting sphincter of Oddi activity

Abstract

The sphincter of Oddi has basal myogenic phasic activity that is modulated by neural and hormonal pathways. Stimulatory innervation to this organ is cholinergic, whereas the inhibitory pathways are unknown. Nitric oxide (NO), generated from L-arginine, relaxes gastrointestinal smooth muscle in vitro. We, therefore, hypothesized that resting sphincter of Oddi and duodenal motilities are regulated by a NO-mediated inhibitory pathway. In 23 anesthetized prairie dogs, systemic blood pressure and sphincter of Oddi and duodenal motilities were monitored during systemic infusion of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. L-NAME was infused alone and simultaneously with excess D- and L-arginine. L-NAME alone and L-NAME with D-arginine produced hypertension and increased sphincter of Oddi and duodenal motilities. L-arginine blocked these increases, suggesting that baseline sphincter of Oddi and duodenal motility regulation involves the generation of NO from L-arginine. We conclude that baseline sphincter of Oddi phasic activity is regulated by cholinergic stimulatory and NO-mediated inhibitory neural pathways.