Release of nitric oxide in the central nervous system mediates tonic and phasic contraction of the cat lower oesophageal sphincter

Nitric oxide (NO) in the brainstem is implicated in the control of swallowing and oesophageal peristalsis. This study examines the role of brainstem NO in the maintenance of lower oesophageal sphincter (LOS) tone, relaxation and contraction. In urethane-anaesthetized cats, oesophageal peristalsis and sphincter pressures were continuously monitored. Drugs were administered into the fourth ventricle. Oesophageal peristalsis and sphincter relaxation and contraction were induced by superior laryngeal nerve stimulation or intra-oesophageal balloon distention. Basal sphincter pressure was significantly reduced after the i.c.v. administration of the nitric oxide synthase (NOS) inhibitor, l-Ng-monomethyl arginine. The inhibitor's d-isomer had no significant effect on basal sphincter pressure, while l-arginine partially reversed the effect. The NOS inhibitor had no effect on sphincter relaxation, whereas the contraction of the sphincter following relaxation was significantly inhibited. Central nitric oxide synthase inhibition reduces basal LOS tone and contraction amplitude but has no effect on swallow or balloon distention induced sphincter relaxation. Therefore, central release of NO acts in the pathway to stimulate dorsal motor nucleus of the vagus neurones projecting to excitatory neurones in the sphincter. Inhibition of nitric oxide synthase in the CNS does not prevent relaxation of the LOS, suggesting that other pathways that do not utilize NO are important in the induction of LOS relaxation.