Excitation of dorsal motor vagal neurons evokes non-nicotinic receptor-mediated gastric relaxation

Vagal stimulation results in both gastric motor excitatory and non-adrenerg ic non-cholinergic (NANC) inhibitory responses. The NANC pathway involves p reganglionic cholinergic neurons, which act through nicotinic receptors to ultimately evoke gastric smooth muscle relaxation via release of nitric oxi de (NO) and other neurotransmitters. Within the dorsal motor nucleus of the vagus (DMN), some preganglionic neurons also contain NO synthase. The NO s ynthase-containing neurons innervate the gastric fundus where adaptive rela xation occurs. This study tests the hypothesis that chemical stimulation of vagal motor neurons in animals, in which nicotinic receptors are blocked, evokes an NO-dependent gastric relaxation. A cell body excitant, N-methyl-D -aspartate (NMDA, 0.03-3 nmol), was microinjected into the DMN in anestheti zed rats while recording intragastric pressure (IgP). The first group recei ved NMDA before and after administration of a ganglionic blocker, hexametho nium bromide (15 mg/kg, i.v.) and atropine (1.0 mg/kg). Significant dose-de pendent increases in IgP and gastric motility occurred before hexamethonium after the 0.3 and 3 nmol doses of NMDA. After hexamethonium, 0.3 and 3 nmo l NMDA evoked significant decreases in IgP. A second group of rats was hexa methonium-pretreated and received NMDA microinjection into the DMN before a nd after an NO synthase inhibitor, N-G-nitro-L-arginine methyl ester (10 mg /kg, i.v.). The NMDA-evoked decrease in IgP was completely abolished by the NO synthase inhibitor. These data support the novel idea that NO synthase- containing preganglionic neurons mediate gastric relaxation that is indepen dent of nicotinic receptors. (C) 1999 Elsevier Science B.V. All rights rese rved.