INFLUENCE OF N(G)-NITRO-L-ARGININE METHYL-ESTER ON VAGALLY INDUCED GASTRIC RELAXATION IN THE ANESTHETIZED RAT

1 The influence of the nitric oxide (NO) biosynthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on the gastric relaxation induced by peripheral vagal stimulation was investigated in the anaesthetized rat. 2 Peripheral vagal stimulation (10 Hz, 10 V, 1 ms for 20 s) induced a reproducible biphasic response: a short-lasting increase followed by a more pronounced decrease in intragastric pressure. This response also occurred in reserpinized animals (5 mg kg-1, i.p., 24 h before the experiment) while atropine (1 mg kg-1, i.v.) abolished the initial increase in intragastric pressure. 3 L-NAME (1-30 mg kg-1, i.v.) induced an increase in arterial blood pressure. L-NAME (1 mg kg-1, i.v.) had no influence on the vagally induced gastric response while L-NAME (10 and 30 mg kg-1 i.v.) significantly changed it: the initial increase in intragastric pressure was enhanced while the decrease in intragastric pressure was reduced or abolished. N(G)-nitro-L-arginine (L-NNA, 10 mg kg-1, i.v.) had the same effect. 4 An i.v. infusion of phenylephrine (10-mu-g kg-1 min-1) inducing a pressor response similar to that produced by L-NAME (30 mg kg-1, i.v.) did not influence the vagal gastric response. Infusion of L-arginine (300 mg kg-1 bolus, then 100 mg kg-1 h-1) starting 30 min beforehand, reduced the pressor effect and prevented the influence of L-NAME (10 mg kg-1, i.v.) on the vagal gastric response. After injection of both atropine (1 mg kg-1, i.v.) and L-NAME (30 mg kg-1, i.v.), the vagally induced decrease in intragastric pressure was similar to that obtained under control conditions. 5 These results are consistent with NO being released and inducing gastric relaxation during peripheral vagal stimulation. In addition to NO, another inhibitory non-adrenergic non-cholinergic neurotransmitter is released.