RESPONSES OF THE RAT LOWER ESOPHAGEAL SPHINCTER (LOS) TO VAGAL EFFERENT ACTIVATION

Nitric oxide (NO) is a major candidate in vagal-induced LOS relaxation . Vagal adrenergic fibres also innervate the gastrointestinal tract in cluding the LOS. This study investigates the role of these two and oth er mechanisms in LOS responses to vagal activation in the rat, and pro vides functional and anatomical evidence for a smooth muscle LOS in th is species. LOS, gastric and oesophageal pressures were measured in ur ethane anaesthetized rats during vagal stimulation. The LOS pressure ( LOSP) response to vagal stimulation (5 mA, 10 Hz, 0.5 msec pulses, 5 s ec) comprised three consecutive stages: (I) brief reduction of LOSP, ( 2) transient increase of LOSP and (3) prolonged reduction of LOSP. The influences of additive treatment with several antagonist drugs on the LOS response to vagal stimulation were investigated. L-NAME (100 mg k g(-1)) reduced stage 1 and increased stage 2. Subsequent treatment wit h either phentolamine (2 mg kg(-1)) or prazosin (200 mu g kg(-1)) abol ished stage 1. After phentolamine, atropine treatment (400 mu g kg(-1) ) abolished stage 2. Stage 3 was evident throughout experiments. In fi ve additional studies, treatment with hexamethonium (30 mg kg(-1)) abo lished stages 2 and 3 leaving stage 1, which was later abolished by ph entolamine or atropine. In the LOS response to vagal stimulation, the following major mechanisms are therefore evident: nicotinic transmissi on in both excitation and inhibition, alpha-adrenergic and NO-mediated inhibition, muscarinic excitation, and non-adrenergic, non-NO inhibit ion (not characterized further). Characteristics of these different ne urotransmitter influences may be important in LOS relaxation associate d with swallowing and gastro-oesophageal reflux.