The role of nitric oxide in non-adrenergic non-cholinergic relaxation in the guinea-pig gastric fundus

The role of nitric oxide (NO) in non-adrenergic non-cholinergic (NANC) neurotransmission was studied on circular muscle strips of the dorsal part of the guinea-pig gastric fundus. In the presence of atropine and guanethidine, a low frequency of electrical stimulation (1≈10 Hz) induced frequency-dependent relaxation which were not affected by adrenergic and cholinergic blockage but abolished by tetrodotoxin. N^G-nitro-L-arginine (L-NNA), a stereospecific inhibitor of NO-biosynthesis, inhibited the relaxations induced by electrical stimulations but not the relaxations to exogenous nitric oxide. The effect of L-NNA was prevented by L-arginine, the precursor of the NO biosynthesis but not by its enantiomer, D-arginine. Exogenous administration of NO caused concentration-dependent relaxations which showed a similarity to those obtained with electrical stimulation. Hemoglobin, a NO scavenger, abolished the NO-induced relaxations and also markedly reduced those induced by electrical stimulation. The inhibitory effect of hemoglobin was similar to that of L-NNA. Application of ATP caused weak relaxations compared with those to electrical stimulation, which were unaffected by L-NNA. Exogenously applied vasoactive intestinal polypeptide (VIP) induced concentration-dependent relaxation which was not affected by L-NNA. These results suggest that NO is produced and released mainly as a neurotransmitter from enteric neurons during NANC relaxation induced by low frequencies and short trains of electrical stimulation and has a main role in NANC neurotransmission at relaxation induced by these electrical stimulations in the guinea-pig gastric fundus.