Pharmacological Features of Non-adrenergic Non-cholinergic (NANC) Relaxation Induced by Electrical Vagal Stimulation in Isolated Mouse Stomach

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Abstract
The non-adrenergic non-cholinergic (NANC) relaxatory response in mouse isolated whole stomach was investigated by electrical vagal stimulation (EVS) to clarify whether nitric oxide (NO) mediates vagal NANC transmission. The stomach was mounted in an organ bath, and the intragastric pressure was measured. Dual electrodes were placed on the esophagus. In the presence of atropine, propranolol and phentolamine, EVS induced a marked gastric relaxation. The response was frequency-dependent, and reproducible by repeated stimulation. The response was blocked by hexamethonium and NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, and significantly depressed by methylene blue, a soluble guanylate cyclase inhibitor, but not by hemoglobin, a radical trapping agent. The inhibitory effect of L-NNA was reversed by L-arginine, a substrate for NO synthase, but not by D-arginine. Exogenous NO caused a relaxation that was inhibited by hemoglobin and methylene blue, but not by L-NNA. The electrical field stimulation also elicited a gastric relaxation that was inhibited by L-NNA and methylene blue, but not by hexamethonium and hemoglobin. These results suggest that the inhibitory NANC response to EVS in the mouse stomach is largely mediated by release of NO, and it is exclusively due to stimulation of vagal preganglionic neurons.