Nitric oxide regulates peptide release from parasympathetic nerves and vascular reactivity to vasoactive intestinal...

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, NG-nitro-L-arginine. The atropine-resistant vasodilation 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 NG-nitro-L-arginine. Furthermore, peptide release from the gland elicited by nerve stimulation was attenuated after NG-nitro-L-arginine administration. Addition of the NO donor, nitroprusside, reversed the NG-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 NG-nitro-L-arginine. Furthermore, the NG-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.