Cholinergic-nitrergic interactions in the guinea pig gastric fundus

The influence of nitric oxide (NO) on the spontaneous tone and on the contractile responses to electrical field stimulation or to exogenous acetylcholine (ACh) was studied. Circular strips from the guinea-pig gastric fundus were used. The NO-releasing compound sodium nitroprusside reduced the spontaneous tone while the NO-synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) increased it. The L-NAME-induced increase of the tone was antagonized by atropine or indomethacin, suggesting the involvement of cholinergic and prostaglandinergic pathways in this effect. L-NAME significantly potentiated the ACh (10(-8) to 10(-5) M)-induced contractions. L-NAME concentration-dependently potentiated the cholinergic contractions evoked by electrical field stimulation without affecting [H-3]ACh overflow from [H-3]choline-treated tissues. It is concluded that electrical field stimulation of gastric fundus muscle induces the release of endogenous nitrate which, in turn, functionally antagonizes cholinergic neurotransmission.