INVOLVEMENT OF THE L-ARGININE - NITRIC-OXIDE PATHWAY IN NONADRENERGICNONCHOLINERGIC RELAXATION OF THE CAT GASTRIC FUNDUS

Vasoactive intestinal polypeptide (VIP) is a neurotransmitter of nonad renergic noncholinergic (NANC) nerves in the cat gastric fundus. A pos sible additional role for nitric oxide (NO) was investigated in circul ar and longitudinal muscle strips from this tissue. Incubation with th e inhibitor of NO-synthesis, N(G)-nitro-L-arginine methyl ester (L-NAM E, 3 x 10(-4) M), inhibited the relaxant response to both short- and l ong-lasting electrical field stimulation. The substrate for NO synthes is, L-arginine (2 x 10(-3) M), prevented this inhibition. In experimen ts with long-lasting electrical field stimulation, trypsin (3 x 10(-6) M) and L-NAME inhibited the beginning of the NANC relaxation to the s ame extent, but the inhibition by trypsin was more pronounced at the e nd of the stimulation period. The inhibitory effect Of L-NAME and tryp sin was additive. L-NAME did not influence the relaxations induced by VI P (10(-7) M), NO (10(-5) M) and isoprenaline (3 x 10(-6) M). N(G)-n itro-L-arginine (3 x 10(-4) M) also did not change the response to VIP . The relaxation induced by 10(-5) M NO was not transient but was sust ained. The plateau phase of this relaxation was reduced by trypsin but not by 3 x 10(-6) M tetrodotoxin. It is concluded that NO is involved in NANC relaxation of the cat gastric fundus. During sustained NANC r elaxation in the cat gastric fundus, cotransmission of NO and VIP is p ossible.