NITRIC-OXIDE MEDIATING NANC INHIBITION IN OPOSSUM LOWER ESOPHAGEAL SPHINCTER

Strips from opossum lower esophageal sphincter were prepared and mounted in organ baths for recording of isometric tension. Nonadrenergic, noncholinergic inhibitory responses were evoked by transmural field stimulation. The relaxant responses to field stimulation were inhibited in a concentration-dependent manner by N-omega-nitro-L-arginine (L-NNA), a substance known to inhibit the formation of nitric oxide (NO). At a concentration at 10(-4) M of L-NNA, most preparations contracted during field stimulation, and this response was abolished by atropine (10(-6) M). L-Arginine (10(-5) M) shifted the concentration-response curve for L-NNA to the right. Relaxant responses to VIP (10(-9) to 10(-6) M) and sodium nitroprusside (10(-9) to 10-5 M) were unaffected by preincubation with L-NNA (10(-5) to 10(-4) M) or L-arginine (10(-5) M). The inhibition of NANC-relaxation was apparently not due to an influence on release of a NANC transmitter different from NO, since L-NNA had no preserving effects on responses to field stimulation in preparations treated with scorpion venom. We conclude that involvement of a NO-generating process from L-arginine seems mandatory for NANC responses in the isolated lower esophageal sphincter.