VAGAL AND SYMPATHETIC INFLUENCES ON THE FERRET LOWER ESOPHAGEAL SPHINCTER

This study has investigated the relative involvement of cholinergic, a drenergic, nitric oxide and tachykininergic transmission in extrinsic neural influences on the lower oesophageal sphincter (LOS) in urethane anaesthetized ferrets. A micromanometric assembly (OD 1.75 mm) incorp orating a sleeve sensor was used for high-fidelity oesophageal, LOS an d gastric pressure measurement at low perfusion rates (< 0.1 ml/min). The LOS response to vagal and splanchnic nerve stimulation (0.5 ms pul se width, 10 s duration) was frequency- and voltage-dependent. LOS res ponses to stimulation at 20 V, 10 Hz were investigated in separate gro ups of animals with either L-NAME (100 mg/kg), hexamethonium (15 mg/kg ), guanethidine (5 mg/kg), CP96,345 (NK-1 antagonist, 4 mg/kg), atropi ne (0.4 mg/kg) or propranolol (1 mg/kg). Propranolol treatment was fol lowed by yohimbine (1 mg/kg) and prazosin (0.25 mg/kg). Vagal stimulat ion caused an immediate decrease in LOS pressure, followed by increase on cessation of stimulation, followed by a prolonged decrease (77 +/- 2%) for up to 5 min. L-NAME did not affect inhibition, but increased excitation 4-fold (p < 0.001). Guanethidine and CP96,345 had no major effect. Hexamethonium decreased the inhibitory (p < 0.05) and excitato ry (p < 0.01) responses. Atropine reduced the excitatory response (p < 0.05). Some inhibition still remained if all treatments were combined . Splanchnic stimulation reduced LOS pressure by 70 +/- 6% for 101 +/- 17 s. L-NAME, guanethidine, hexamethonium and CP96,345 all independen tly significantly reduced inhibition. The combination of guanethidine and CP96,345 usually abolished splanchnic-induced inhibition. Atropine was without effect. Propranolol (1 mg/kg) changed the splanchnic-indu ced response from mainly inhibition to excitation (100 +/- 44% increas e). LOS responses to noradrenaline (1-10 mu g close IA) showed similar features to responses to splanchnic stimulation. We conclude that vag al stimulation evokes LOS relaxation via activation of established cho linergic and NANC mechanisms and other, unidentified mechanisms. Splan chnic stimulation activates adrenergic neurones probably via nicotinic and non-nicotinic ganglionic mechanisms, which in turn elicit beta ad renergic inhibitory effects on the LOS. Splanchnic stimulation also an tidromically activates spinal afferent fibres. These may release subst ance P from peripheral myenteric plexus and prevertebral ganglionic en dings causing activation of myenteric NANC inhibitory neurones and sym pathetic neurones, respectively. (C) 1997 Elsevier Science B.V.