PHARMACOLOGICAL FEATURES OF NONADRENERGIC NONCHOLINERGIC (NANC) RELAXATION INDUCED BY ELECTRICAL VAGAL-STIMULATION IN ISOLATED MOUSE STOMACH

The non-adrenergic non-cholinergic (NANC) relaxatory response in mouse isolated whole stomach was investigated by electrical vagal stimulati on (EVS) to clarify whether nitric oxide (NO) mediates vagal NANC tran smission. The stomach was mounted in an organ bath, and the intragastr ic pressure was measured. Dual electrodes were placed on the esophagus . In the presence of atropine, propranolol and phentolamine, EVS induc ed a marked gastric relaxation. The response was frequency-dependent, and reproducible by repeated stimulation. The response was blocked by hexamethonium and N-G-nitro-L-arginine (L-NNA), a NO synthase inhibito r, and significantly depressed by methylene blue, a soluble guanylate cyclase inhibitor, but not by hemoglobin, a radical trapping agent. Th e inhibitory effect of L-NNA was reversed by L-arginine, a substrate f or NO synthase, but not by D-arginine. Exogenous NO caused a relaxatio n that was inhibited by hemoglobin and methylene blue, but not by L-NN A. The electrical field stimulation also elicited a gastric relaxation that was inhibited by L-NNA and methylene blue, but not by hexamethon ium and hemoglobin. These results suggest that the inhibitory NANC res ponse to EVS in the mouse stomach is largely mediated by release of NO , and it is exclusively due to stimulation of vagal preganglionic neur ons.