Transmitter mechanisms in vagal afferent-induced reduction of lower oesophageal sphincter (LOS) pressure in the rat.
The extrinsic neural pathways and transmitter mechanisms involved in neural influences controlling lower oesophageal sphincter (LOS) pressure have been evaluated in three groups of experiments in urethane anaesthetized rats. A miniature perfused sleeve/sidehole catheter measured gastric, LOS and oesophageal pressures. Group 1: Vago-vagal and vago-spinal reflex pathways were activated simultaneously via the central nervous system by stimulation of the central cut end of the left vagus. This caused a prolonged drop in LOS pressure with a rapid onset and a slow return to baseline. Subsequent right (bilateral) vagotomy in these animals increased basal LOSP (P < 0.001). Central vagal stimulation-induced reduction of LOSP was not significantly changed in amplitude but was shorter in duration (P < 0.01) than before bilateral vagotomy. IV administration of the 5-HT3 receptor antagonist granisetron (50 micrograms/kg), after bilateral vagotomy had no effect on the response to central vagal stimulation. The nitric oxide (NO) synthase inhibitor L-nitroarginine methyl ester (L-NAME) (100 mg/kg) reduced the depth of relaxation (P < 0.01) and temporarily increased basal LOSP. Propranolol (1.5 mg/kg, i.v.) subsequently increased basal LOSP (P < 0.01), but had no further effect on the vagal stimulation-induced reduction in LOSP. Alpha adrenergic blockade with phentolamine (1 mg/kg, i.v.) decreased basal LOSP (P < 0.01), and nearly abolished the response to vagal stimulation (P < 0.01). Group 2: Both alpha 1- and alpha 2-adrenoceptors were shown to be involved by the combined use of the more selective antagonists yohimbine (1 mg/kg, i.v.) and prazosin (200 micrograms/kg) in place of phentolamine. Group 3: To observe neurotransmitter mechanisms in the vago-vagal pathway, central left vagal stimulation was performed after left vagotomy, and subsequently after blockade of sympathetic motor pathways with guanethidine (5 mg/kg), leaving intact efferent pathways in the right vagus. Guanethidine increased basal LOSP (P < 0.01), and reduced the duration of vagal-induced LOS relaxation (P < 0.05). Depth of relaxation was unchanged. Subsequently, granisetron and L-NAME had no significant effects. Finally, additional right vagotomy abolished the remaining response. Our data indicate the existence of vago-spinal and vago-vagal inhibitory reflex pathways to the rat LOS. The inhibitory vago-spinal pathway is mainly alpha-adrenergic, and has a minor NO-mediated component, but no 5-HT3 receptor-mediated mechanism. In the vago-vagal pathway, no significant involvement of NO-mediated or 5-HT3 receptor-mediated effects was observed. Other non-adrenergic inhibitory mechanisms were, however, apparent.(ABSTRACT TRUNCATED AT 400 WORDS)
Kawahara
H
H
Gastroenterology Unit, Royal Adelaide Hospital, Australia.
Blackshaw
L A
LA
Nisyrios
V
V
Dent
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004943:Esophagogastric Junction / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008297:Male; D008365:Manometry; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018377:Neurotransmitter Agents; D012702:Serotonin Antagonists; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester