NITRIC-OXIDE REGULATES PEPTIDE RELEASE FROM PARASYMPATHETIC NERVES AND VASCULAR REACTIVITY TO VASOACTIVE INTESTINAL POLYPEPTIDE IN-VIVO

The possible involvement of nitric oxide (NO) in the vasodilator respo nse to parasympathetic nerve stimulation in the pig submandibular glan d in vivo was studied using the NO synthase inhibitor, N-G-nitro-L-arg inine. The atropine-resistant vasodilatation elicited by parasympathet ic stimulation (10 Hz, 30 s) and the response elicited by i.v. injecti on of vasoactive intestinal polypeptide (VIP) were markedly reduced by N-G-nitro-L-arginine. Furthermore, peptide release from the gland eli cited by nerve stimulation was attenuated after N-G-nitro-L-arginine a dministration. Addition of the NO donor, nitroprusside, reversed the N -G-nitro-L-arginine evoked attenuation of the response to nerve stimul ation and VIP. Also the cholinergic parasympathetic component and the vascular effect of acetylcholine were reduced by N-G-nitro-L-arginine. Furthermore, the N-G-nitro-L-arginine-induced attenuation of the vasc ular responses was partially prevented by milrinone, an inhibitor of t he cyclic GMP-regulated phosphodiesterase III. The present results sug gest that NO may be crucial for parasympathetic vasodilatation by regu lating peptide release and second messenger systems for VIP and acetyl choline.