Release of nitric oxide upon stimulation of nonadrenergic noncholinergic nerves in the rat gastric fundus

Abstract

The possible role of nitric oxide (NO) as inhibitory nonadrenergic noncholinergic (NANC) neurotransmitter was studied in the rat gastric fundus. NO induced tetrodotoxin-resistant NANC relaxations in longitudinal muscle strips similar to those induced by electrical stimulation. Incubation with the stereospecific inhibitors of the NO biosynthesis NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (L-NNA) resulted in an increase of the basal tension which was reversed partly by L-arginine, but not by D-arginine. L-NMMA and L-NNA inhibited the relaxations to electrical stimulation, but not those induced by ATP, vasoactive intestinal polypeptide (VIP), norepinephrine or NO. This inhibitory effect was prevented by L-arginine, but not by D-arginine. In a second series of experiments, the gastric fundus served as donor tissue in a superfusion bioassay with de-endothelialized rings of rabbit aorta as detector tissue. The fundus released a labile factor with vasodilator activity upon electrical stimulation. This release was inhibited by tetrodotoxin and L-NNA, whereas it was increased by L-arginine. The biological activity was enhanced by superoxide dismutase and eliminated by hemoglobin. Our results indicate that NO is formed and released upon brief stimulation of the NANC nerves in the rat gastric fundus which is essential for the transient relaxations in this preparation. Therefore, we suggest NO or a NO releasing substance as inhibitory NANC transmitter in the rat gastric fundus.