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Innervation of lower airways and neuropeptide effects on bronchial and vascular tone in the pig

Cell and Tissue Research volume 260, pages 223–233 (1990)Cite this article

Summary

The occurrence and distribution of peptide-containing nerve fibres [substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY)] and noradrenergic nerve fibres [tyrosine hydroxylase (TH)- and dopamine beta hydroxylase (DBH)-positive] in the airways of the pig were studied by means of immunohistochemistry. SP- and CGRP-immunoreactive (-IR) nerve fibres were present close to and within the lining respiratory epithelium, around blood vessels, within the tracheobronchial smooth muscle layer and around local tracheobronchial ganglion cells. The content of CGRP- and neurokinin A (NKA)-like immunoreactivity (-LI) measured by radioimmunoassay (RIA) was twice as high in the trachea compared to that in the peripheral bronchi. SP was a more potent constrictor agent than NKA on pig bronchi in vitro. CGRP had a relaxant effect on precontracted pig bronchi. On blood vessels CGRP exerted a relaxant effect that was more pronounced on pulmonary arteries than on bronchial arteries. VIP/PHI-IR fibres were seen in association with exocrine glands and in the tracheobronchial smooth muscle layer. VIP-positive nerve fibres were abundant around blood vessels in the trachea but sparse or absent around blood vessels in the peripheral bronchi. This histological finding was supported by RIA; it was shown that the content of peptides displaying VIP-like immunoreactivity (-LI) was 18 times higher in the trachea compared to peripheral bronchi. VIP was equally potent as CGRP in relaxing precontracted pig bronchi in vitro. Both bronchial and pulmonary arteries were relaxed by VIP. NPY was colocalized with VIP in tracheal periglandular nerve fibres and in nerve fibres within the tracheobronchial smooth muscle layer. NPY was also present in noradrenergic (DBH-positive) vascular nerve fibres. The content of NPY was much higher (15-fold) in the trachea compared to small bronchi. NPY caused a contraction of both pulmonary and bronchial arteries. The bronchial smooth muscle contraction to field stimulation in vitro was purely cholinergic. A non-cholinergic relaxatory effect following field stimulation was observed after bronchial precontraction. Capsaicin had no effect on pig bronchi in vitro.

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References

  • Baier H, Long WM, Wanner A (1985) Bronchial circulation in asthma. Respiration 48:199–205

    Google Scholar 

  • Barnes PJ, Basbaum CB, Nadel JA (1983) Autoradiogrpahic localization of autonomic receptors in airway smooth muscle. Marked differences between large and small airways. Am Rev Respir Dis 127:758–762

    Google Scholar 

  • Brodin E, Lindefors N, Dalsgaard C-J, Theodorsson-Norheim E, Rosell S (1986) Tachykinin multiplicity in rat central nervous system as studied using antisera raised against substance P and neurokinin A. Regul Pept 13:253–272

    Google Scholar 

  • Cadieux A, Springall DR, Mulderry PK, Rodrigo J, Ghatei MA, Terenghi G, Bloom SR, Polak JM (1986) Occurrence, distribution and ontogeny of CGRP immunoreactivity in the rat lower respiratory tract: effect of capsaicin treatment and surgical denervations. Neuroscience 19:605–627

    Google Scholar 

  • Calka W (1975) Vascular supply of the lungs through direct branches of the aorta in domestic pig. Folia Morphol (Warsz) 34:135–142

    Google Scholar 

  • Cameron AR, Johnston CF, Kirkpatrick CT, Kirkpatrick MCA (1983) The quest for the inhibitory transmitter in bovine tracheal smooth muscle. Q J Exp Physiol 68:413–426

    Google Scholar 

  • Campbell G (1971) Autonomic innervation of the lung musculature of a toad (Bufo marinus). Comp Gen Pharmacol 2:281–286

    Google Scholar 

  • Collier PS (1979) Bronchial arteries of the dog. A pharmacoanatomical study. J Anat 128:887–888

    Google Scholar 

  • Cudkowicz L, Armstrong JB (1951) Observations on the normal anatomy of the bronchial arteries. Thorax 6:343–358

    Google Scholar 

  • Cuello AC, Galfree G, Milstein C (1979) Detection of substance P in nervous system by a monoclonal antibody. Proc Natl Acad Sci USA 76:3532–3536

    Google Scholar 

  • Deffebach ME, Charan NB, Lakshminarayan S, Butler J (1987) The bronchial circulation. Small but vital attribute of the lung. Am Rev Resp Dis 135:463–481

    Google Scholar 

  • Fahrenkrug J, Schaffalitzky de Muckadell OB (1978) Distribution of vasoactive intestinal polypeptide in the porcine central nervous system. J Neurochem 31:1445–1451

    Google Scholar 

  • Fahrenkrug J, Galbo H, Holst JJ, Schaffalitzky de Muckadell OB (1978) Influence of the autonomic nervous system on the release of vasoactive intestinal polypeptide from the porcine gastrointestinal tract. J Physiol (Lond) 280:405–422

    Google Scholar 

  • Hua X-Y, Theordorsson-Norheim E, Brodin E, Lundberg JM, Hökfelt T (1985) Multiple tachykinins (neurokinin A, neuropeptide K and substance P) in capsaicin-sensitive sensory nerves in the guinea-pig. Regul Pept 13:1–19

    Google Scholar 

  • Hökfelt T, Fuxe K, Goldstein M, Joh TH (1973) Immunohistochemical localization of three catecholamines synthetizing enzymes: aspect on methodology. Histochemie 33:231–236

    Google Scholar 

  • Ito Y, Takeda K (1982) Non-adrenergic inhibitory nerves and putative transmitters in the smooth muscle of the trachea. J Physiol (Lond) 330:497–511

    Google Scholar 

  • Lacroix JS (1989) Adrenergic and non-adrenergic mechanisms in sympathetic vascular control of the nasal mucosa. Acta Physiol Scand 136 (Suppl 581):1–63

    Google Scholar 

  • Lundberg JM (1981) Evidence for coexistence of vasoactive intestinal polypeptide (VIP) and acetylcholine in neurons of cat exocrine glands. Morphological, biochemical and functional studies. Acta Physiol Scand 112 (Suppl 496):1–57

    Google Scholar 

  • Lundberg JM, Hökfelt T, Änggård A, Terenius L, Elde R, Markey K, Goldstein M, Kimmel J (1982a) Organizational principles in the peripheral sympathetic nervous system: Subdivision by co-existing peptides (somatostatin, avian pancreatic polypeptide and vasoactive intestinal polypeptide-like immunoreactive materials). Proc Natl Acad Sci USA 79:1302–1307

    Google Scholar 

  • Lundberg JM, Terenius L, Hökfelt T, Martling C-R, Tatemoto K, Mutt V, Polak JM, Bloom SR, Goldstein M (1982b) Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand 116:477–480

    Google Scholar 

  • Lundberg JM, Hökfelt T, Martling C-R, Saria A, Cuello C (1984a) Substance P-immunoreactive sensory nerves in the lower respiratory tract of various mammals including man. Cell Tissue Res 235:251–261

    Google Scholar 

  • Lundberg JM, Fahrenkrug J, Hökfelt T, Martling C-R, Larsson O, Tatemoto K, Änggård A (1984b) Co-existence of peptide HI and VIP in nerves regulating blood flow and bronchial smooth muscle tone in various mammals including man. Peptides 5:593–606

    Google Scholar 

  • Lundberg JM, Terenius L, Hökfelt T, Tatemoto K (1984c) Comparative immunohistochemical and biochemical analysis of pancreatic polypeptide-like peptides with special reference to presence of neuropeptide Y in central and peripheral neurons. J Neurosci 4:2376–2386

    Google Scholar 

  • Lundberg JM, Franco-Cereceda A, Hua X-Y, Hökfelt T, Fischer JA (1985) Co-existence of substance P and calcitonin gene related peptide-like immunoreactivities in sensory nerves in relation to cardiovascular and bronchoconstrictor effects of capsaicin. Eur J Pharmacol 108:315–319

    Google Scholar 

  • Lundberg JM, Martling C-R, Hökfelt T (1988) Airways, oral cavity and salivary glands: classical transmitters and peptides in sensory and autonomic motor neurons. In: Björklund A, Hökfelt T, Owman C (eds) Handbook of chemical neuroanatomy, Vol 6: The peripheral nervous system. Elsevier, Amsterdam, pp 391–444

    Google Scholar 

  • Magno MG, Fishman AP (1982) Origin, distribution, and blood flow of bronchial circulation in anesthetized sheep. J Appl Physiol 53:272–279

    Google Scholar 

  • Markey KA, Kondo S, Shenkman L, Goldstein M (1984) Purification and characterization of tyrosine hydroxylase from a clonal pheochromocytoma cell line. Mol Pharmacol 17:204–213

    Google Scholar 

  • Martling C-R (1987) Sensory nerves containing tachykinins and CGRP in the lower airways. Functional implications for bronchoconstriction, vasodilatation and protein extravasation. Acta Physiol Scand 130 (Suppl 563):1–57

    Google Scholar 

  • Martling C-R, Theodorsson-Norheim E, Lundberg JM (1987a) Occurrence and effects of multiple tachykinins; substance P, neurokinin A and neuropeptide K in human lower airways. Life Sci 40:1633–1643

    Google Scholar 

  • Martling C-R, Änggård A, Lundberg JM (1985) Non-cholinergic vasodilation in the tracheobronchial tree of the cat induced by vagal nerve stimulation. Acta Physiol Scand 125:343–346

    Google Scholar 

  • Martling C-R, Gazelius B, Lundberg JM (1987b) Nervous control of tracheal blood flow in the cat measured by the laser Doppler technique. Acta Physiol Scand 130:409–417

    Google Scholar 

  • Martling C-R, Saria A, Fischer JA, Hökfelt T, Lundberg JM (1988) Calcitonin gene-related peptide and the lung: neuronal coexistence with substance P, release by capsaicin and vasodilatory effect. Regul Pept 20:125–139

    Google Scholar 

  • Martling C-R, Matran R, Alving K, Lacroix JS, Lundberg JM (1989) Vagal vasodilatory mechanisms in the pig bronchial circulation preferentially involves sensory nerves. Neurosci Lett 96:306–311

    Google Scholar 

  • Matran R, Alving K, Martling C-R, Lacroix JS, Lundberg JM (1989a) Vagally mediated vasodilatation by motor and sensory nerves in the tracheal and bronchial circulation of the pig. Acta Physiol Scand 135:29–37

    Google Scholar 

  • Matran R, Alving K, Martling C-R, Lacroix JS, Lundberg JM (1989b) Effects of neuropeptides and capsaicin on tracheobronchial blood flow of the pig. Acta Physiol Scand 135:335–342

    Google Scholar 

  • Matsuzaki Y, Hamasaki Y, Said S (1980) Vasoactive intestinal peptide: a possible transmitter of nonadrenergic relaxation of guinea pig airways. Science 210:1252–1253

    Google Scholar 

  • Nilsson G, Dahlberg K, Brodin E, Sundler F, Strandberg K (1977) Distribution and constrictor effects of substance P in guinea pig tracheobronchial tissue. In: Euler US von, Pernow B (eds) Substance P. Raven Press, New York, pp 57–61

    Google Scholar 

  • Palmer JBD, Cuss FMC, Mulderry PK, Ghatei MA, Springall DR, Cadieux A, Bloom SR, Polak JM, Barnes PJ (1987) Calcitonin gene-related peptide is located to human airway nerves and potently constricts human airway smooth muscle. Br J Pharmacol 91:95–101

    Google Scholar 

  • Peatfield AC, Richardson PS (1983) Evidence for non-cholinergic, non-adrenergic nervous control of mucus secretion into the cat trachea. J Physiol (Lond) 342:335–345

    Google Scholar 

  • Peatfield AC, Barnes PJ, Bratcher C, Nadel JA, Davis B (1983) Vasoactive intestinal peptide stimulates tracheal submucosal gland secretion in ferret. Am Rev Respir Dis 128:89–93

    Google Scholar 

  • Pump KK (1972) Distribution of bronchial arteries in the human lung. Chest 62:447–451

    Google Scholar 

  • Richardson J, Beland J (1976) Nonadrenergic inhibitory nervous system in human airways. J Appl Physiol 41:764–771

    Google Scholar 

  • Said SI, Mutt V (1970) Polypeptide with broad biological activity. Isolation from small intestine. Science 169:1217–1218

    Google Scholar 

  • Said SI, Mutt V (1977) Relationships of spasmogenic and smooth muscle relaxant peptide from normal lung to other vasoactive components. Nature 265:84–86

    Google Scholar 

  • Stuart-Smith K, Vanhoutte PM (1988) Airway epithelium modulates the responsiveness of porcine bronchial smooth muscle. J Appl Physiol 65:721–727

    Google Scholar 

  • Theodorsson-Norheim E, Hemsén A, Lundberg JM (1985) Radioimmunoassay for neuropeptide Y (NPY): chromatographic characterization of immunoreactivity in plasma and tissue extracts. Scand J Clin Lab Invest 45:355–365

    Google Scholar 

  • Turk GM, Charan NB, Czartolomny J (1985) Systemic arterial blood supply to the lung in sheep. Fed Proc 44:1757

    Google Scholar 

  • Uddman R, Luts A, Sundler F (1985) Occurrence and distribution of calcitonin gene-related peptide in the mammalian respiratory tract and middle ear. Cell Tissue Res 241:551–555

    Google Scholar 

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Affiliations

  1. Department of Anaesthesia, Karolinska Hospital, Stockholm, Sweden

    C.-R. Martling

  2. Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden

    R. Matran, K. Alving & J. M. Lundberg

  3. Department of Histology, Karolinska Institutet, Stockholm, Sweden

    T. Hökfelt

Authors
  1. C.-R. Martling
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  2. R. Matran
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  3. K. Alving
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  4. T. Hökfelt
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  5. J. M. Lundberg
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Martling, CR., Matran, R., Alving, K. et al. Innervation of lower airways and neuropeptide effects on bronchial and vascular tone in the pig. Cell Tissue Res 260, 223–233 (1990). https://doi.org/10.1007/BF00318626

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Key words

  • Airway innervation
  • Substance P
  • Calcitonin gene-related peptide
  • Vasoactive intestinal polypeptide
  • Neuropeptide Y
  • Noradrenaline
  • Acetylcholine
  • Pig