title: Nitric oxide synthase in the pig autonomic nervous system in relation to the influence of NG--nitro-L-arginine on sympathetic and parasympathetic vascular control in vivo.
abstract: Nitric oxide synthase, the enzyme responsible for the formation of nitric oxide, was demonstrated by an indirect immunofluorescence technique to be present in both the sympathetic and parasympathetic nervous system of the domestic pig. In the sympathetic nervous system, nitric oxide 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 sympathetic chain. A minor population of postganglionic sympathetic neurons contained nitric oxide synthase, vasoactive intestinal polypeptide and peptide histidine isoleucine. In the densely sympathetically innervated vascular beds such as the spleen, kidney and skeletal muscle, many neuropeptide Y- but no nitric oxide synthase-positive fibres were found. The nitric oxide synthase inhibitor NG-nitro-L-arginine reduced cardiac output by 40% and caused profound vasoconstriction in a variety of vascular beds. Furthermore, no or minor changes in plasma catecholamines, neuropeptide Y or endothelin-1 were observed up to 20 min after NG-nitro-L-arginine. Milrinone (a phosphodiesterase III inhibitor) prevented this NG-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 stimulation, with single impulses of 10 Hz for 1 s in the presence of NG-nitro-L-arginine, evoked vasoconstrictor responses which were largely in the same range as in control conditions. Parasympathetic postganglionic neurons to the submandibular salivary gland contained nitric oxide synthase, 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 NG-nitro-L-arginine administration. Milrinone attenuated the inhibitory effect of NG-nitro-L-arginine on the parasympathetic vasodilation. In conclusion, nitric oxide synthase can be demonstrated in preganglionic sympathetic and postganglionic parasympathetic neurons. The main effect of nitric oxide synthase inhibition seems to be related to attenuation of basal endothelial nitric oxide production and parasympathetic transmission. Inhibition of phosphodiesterase counteracts both the haemodynamic and the neuronal effects of NG-nitro-L-arginine.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Modin
authors.forename: E
authors.initials: E
authors.lastname: Weitzberg
authors.forename: T
authors.initials: T
authors.lastname: Hökfelt
authors.forename: J M
authors.initials: JM
authors.lastname: Lundberg
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000201:enzymology*; D001808:Blood Vessels / Q000294:innervation*; D004558:Electric Stimulation; D007150:Immunohistochemistry; D008161:Lumbosacral Region; D008297:Male; D020105:Milrinone; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D013552:Swine; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D020105:Milrinone