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 response to parasympathetic nerve stimulation in the pig submandibular gland in vivo was studied using the NO synthase inhibitor, N-G-nitro-L-arginine. The atropine-resistant vasodilatation elicited by parasympathetic stimulation (10 Hz, 30 s) and the response elicited by i.v. injection of vasoactive intestinal polypeptide (VIP) were markedly reduced by N-G-nitro-L-arginine. Furthermore, peptide release from the gland elicited by nerve stimulation was attenuated after N-G-nitro-L-arginine administration. Addition of the NO donor, nitroprusside, reversed the N-G-nitro-L-arginine evoked attenuation of the response to nerve stimulation 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 vascular responses was partially prevented by milrinone, an inhibitor of the cyclic GMP-regulated phosphodiesterase III. The present results suggest that NO may be crucial for parasympathetic vasodilatation by regulating peptide release and second messenger systems for VIP and acetylcholine.