Lower oesophageal sphincter relaxation evoked by stimulation of the dorsal motor nucleus of the vagus in ferrets

Abstract

An understanding of the neural control of lower oesophageal sphincter (LOS) relaxation is clinically relevant because transient LOS relaxations (TLOSRs) are a mechanism of acid reflux into the oesophagus. Preganglionic motor neurones innervating the LOS are localized in the dorsal motor nucleus of the vagus (DMV). Based on a single study in cats, it is now widely accepted that these neurones are functionally organized into two separate populations, such that stimulation of the caudal and rostral DMV evokes LOS relaxation and contraction, respectively. Our goal was to map the functional LOS responses to chemical stimulation in the DMV and nucleus tractus solitarius (NTS) of ferrets, an animal model commonly used for conscious studies on TLOSRs, and to test whether DMV-evoked LOS relaxation is mediated through hexamethonium-sensitive vagal-inhibitory pathways to the LOS. We used miniaturized manometry with Dentsleeve to monitor LOS and oesophageal pressures in decerebrate unanaesthetized ferrets. LOS relaxation was evoked readily in response to gastric insufflation, which shows that the vago-vagal reflex was intact in this preparation. Microinjections of l-glutamate (12.5 nmol L-1 in 25 nL) were made into the DMV from approximately - 1.5 to + 2.0 mm relative to the obex. Microinjections into the caudal (- 1.5 to + 0.0 mm behind obex) and intermediate (+ 0.1 to + 1.0 mm rostral to obex) DMV both significantly decreased LOS pressure, and complete LOS relaxation was noted in 28/32 and 11/18 cases, respectively. LOS relaxation responses to DMV microinjection were highly reproducible and abolished by bilateral vagotomy or hexamethonium (15 mg kg-1 intravenously). A nitric oxide synthase inhibitor (l-NAME 100 mg kg-1 intramuscularly) significantly increased the time taken to reach the maximal response. Increases in LOS pressure (24 +/- 4 mmHg; n = 3) were obtained only when stimulation sites were located equal to greater than 1.5 mm rostral to the obex. LOS relaxation (- 78 +/- 10%; n = 6) was evoked by stimulation of the NTS but not immediately outside of the NTS (11 +/- 27%; n = 5). We conclude that there is a very extensive population of 'inhibitory' motor neurones in the DMV that may account for the predominant vagal-inhibitory tone in ferrets. As NTS stimulation evokes LOS relaxation and the predominant response to DMV stimulation is also LOS relaxation, this vago-vagal reflex may involve an excitatory interneurone between the NTS and DMV vagal inhibitory output.

Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

“…Furthermore, brain stem neurons regulating salivary gland function express NOS (63). NOS is present in a portion of vagal preganglionic neurons in the DMV, innervating the low esophageal sphincter, as well as in a subpopulation of vagal motoneurons that project to the gastric fundus, excitation of which evokes low esophageal sphincter and gastric relaxation (1,32,37,62).…”

Orexins in rat dorsal motor nucleus of the vagus potently stimulate gastric motor function

“…Preganglionic neurons in the DMN may be functionally divided into a group rostral to the obex, where stimulation results in upper gastrointestinal excitation, and a more caudal area located behind the obex, where stimulation results in upper gastrointestinal muscle (lower esophageal sphincter) relaxation (1,18). Gastric motor excitation evoked by stimulation of the DMN is abolished by atropine and involves cholinergic preganglionic neurons that synapse onto postganglionic cholinergic neurons.…”

“…We used similar injections of L-glutamate into the DMN caudal to the obex to evoke gastric relaxation before microinjection of orexin A. The relaxation evoked by stimulation of DMN neurons caudal to the obex is thought to be due to activation of vagal neurons that innervate inhibitory nonadrenergicnoncholinergic (NANC) motor neurons (1,18).…”

Review article: the clinical relevance of transient lower oesophageal sphincter relaxations in gastro-oesophageal reflux disease

“…41 However, signals from the NTS do not provide signals to the LOS directly, instead, signals from the NTS are relayed to the dorsal motor nucleus of the vagus (DMV). 42 Motor function of the entire gastrointestinal tract including oesophagus and LOS is modulated by the DMV.…”