Influence of NG-nitro-L-arginine on non-adrenergic non-cholinergic relaxation in the guinea-pig gastric fundus.

1. The influence of NG-nitro-L-Arginine (L-NNA) on non-adrenergic non-cholinergic (NANC) relaxations induced by electrical field stimulation was investigated in circular muscle strips of the guinea-pig gastric fundus. 2. In the presence of 10(-6) M atropine and 4 x 10(-6) M guanethidine, electrical field stimulation (40 V, 1 ms, 0.125-16 Hz) with 10 s trains at 5 min intervals induced short-lasting, frequency-dependent relaxations. Continuous stimulation, with cumulative increase of the stimulation frequency, induced sustained frequency-dependent relaxations. Both types of response were abolished by 3 x 10(-6) M tetrodotoxin. 3. L-NNA (10(-5) M and 10(-4) M) concentration-dependently reduced both types of NANC response. Pre-incubation with 2 x 10(-3) M L-arginine prevented the inhibitory action of 10(-5) M L-NNA and partially antagonized that of 10(-4) M L-NNA. D-arginine (2 x 10(-3) M) did not protect against the inhibitory effect of L-NNA. 4. L-NNA did not consistently influence the basal tone of the tissues. L-Arginine and D-arginine likewise did not influence basal tone; they also had no influence on the electrically-induced NANC relaxations. 5. NO (10(-6)-10(-4) M) induced short-lasting concentration-dependent relaxations, while vasoactive intestinal polypeptide (VIP, (10(-9)-10(-7) M) induced more sustained relaxations, that developed at a slower rate. The NO- and VIP-induced relaxations were not influenced by 10(-4) M L-NNA.6. These results suggest that NO is involved in NANC neurotransmission of the guinea-pig gastric fundus; its contribution to sustained NANC relaxation in the guinea-pig gastric fundus is much more important than in the rat.