Influence of NG-nitro-L-arginine methyl ester on vagally induced gastric relaxation in the anaesthetized 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