NITRIC-OXIDE SYNTHASE IN THE PIG AUTONOMIC NERVOUS-SYSTEM IN RELATIONTO THE INFLUENCE OF N-G-NITRO-L-ARGININE ON SYMPATHETIC AND PARASYMPATHETIC VASCULAR CONTROL IN-VIVO

Nitric oxide synthase, the enzyme responsible for the formation of nit ric oxide, was demonstrated by an indirect immunofluorescence techniqu e to be present in both the sympathetic and parasympathetic nervous sy stem of the domestic pig. In the sympathetic nervous system, nitric ox ide synthase was mainly present in preganglionic neurons projecting to postganglionic neurons, some of which contained neuropeptide Y in the superior cervical, the coeliac and the lumbar ganglia of the sympathe tic chain. A minor population of postganglionic sympathetic neurons co ntained nitric oxide synthase, vasoactive intestinal polypeptide and p eptide histidine isoleucine. In the densely sympathetically innervated vascular beds such as the spleen, kidney and skeletal muscle, many ne uropeptide Y- but no nitric oxide synthase-positive fibres were found. The nitric oxide synthase inhibitor N-G-nitro-L-arginine reduced card iac output by 40% and caused profound vasoconstriction in a variety of vascular beds. Furthermore, no or minor changes in plasma catecholami nes, neuropeptide Y or endothelin-l were observed up to 20 min after N -G-nitro-L-arginine. Milrinone (a phosphodiesterase III inhibitor) pre vented this N-G-nitro-L-arginine-induced reduction in cardiac output, and the regional vasoconstriction was reduced, whereas some elevation of the blood pressure was still observed. Sympathetic nerve stimulatio n, with single impulses of 10 Hz for 1 s in the presence of N-G-nitro- L-arginine, evoked vasoconstrictor responses which were largely in the same range as in control conditions. Parasympathetic postganglionic n eurons to the submandibular salivary gland contained nitric oxide synt hase, vasoactive intestinal polypeptide, peptide histidine isoleucine and neuropeptide Y. The vasodilatation evoked by parasympathetic nerve stimulation (10 Hz for 1 s) in the presence as well as in the absence of atropine was, on the other hand, markedly reduced by N-G-nitro-L-a rginine administration. Milrinone attenuated the inhibitory effect of N-G-nitro-L-arginine on the parasympathetic vasodilatation. In conclus ion, nitric oxide synthase can be demonstrated in preganglionic sympat hetic and postganglionic parasympathetic neurons. The main effect of n itric oxide synthase inhibition seems to be related to attenuation of basal endothelial nitric oxide production and parasympathetic transmis sion. Inhibition of phosphodiesterase counteracts both the haemodynami c and the neuronal effects of N-G-nitro-L-arginine.