Involvement of the L-arginine: nitric oxide pathway in nonadrenergic noncholinergic relaxation of the cat gastric fundus.

Vasoactive intestinal polypeptide (VIP) is a neurotransmitter of nonadrenergic noncholinergic (NANC) nerves in the cat gastric fundus. A possible additional role for nitric oxide (NO) was investigated in circular and longitudinal muscle strips from this tissue. Incubation with the inhibitor of NO-synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 3 x 10(-4) M), inhibited the relaxant response to both short- and long-lasting electrical field stimulation. The substrate for NO synthesis, L-arginine (2 x 10(-3) M), prevented this inhibition. In experiments with long-lasting electrical field stimulation, trypsin (3 x 10(-6) M) and L-NAME inhibited the beginning of the NANC relaxation to the same extent, but the inhibition by trypsin was more pronounced at the end of the stimulation period. The inhibitory effect of L-NAME and trypsin was additive. L-NAME did not influence the relaxations induced by VIP (10(-7) M), NO (10(-5) M) and isoprenaline (3 x 10(-6) M). NG-nitro-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 sustained. 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 relaxation in the cat gastric fundus, cotransmission of NO and VIP is possible.