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. 1989 Nov;62(5):353–360. doi: 10.1136/hrt.62.5.353

A study of nerves containing peptides in the pulmonary vasculature of healthy infants and children and of those with pulmonary hypertension.

K M Allen 1, J Wharton 1, J M Polak 1, S G Haworth 1
PMCID: PMC1224833  PMID: 2686736

Abstract

Nerves containing peptides that supply the human intrapulmonary vasculature were studied in 21 controls aged one month to 24 years and in 13 patients with pulmonary hypertension aged 11 days to eight years. An indirect immunofluorescence technique was used to study the distribution and relative density of nerve fibres containing the general neuronal marker, protein gene product 9.5; tyrosine hydroxylase; synaptophysin; neuropeptide tyrosine; vasoactive intestinal polypeptide; substance P, somatostatin; and calcitonin gene related peptide. At all ages in normal and hypertensive lungs neuropeptide tyrosine was the predominant neuropeptide associated with the pulmonary vascular nerves. In normal lungs the relative density of nerve fibres increased during childhood only in the arteries of the respiratory unit. Pulmonary hypertension was associated with the premature innervation of these arteries during the first year of life. Innervation of small, abnormally thick-walled pre-capillary vessels by predominantly vasoconstrictor nerves may help to explain the susceptibility of infants to pulmonary hypertensive crises.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen K. M., Haworth S. G. Cytoskeletal features of immature pulmonary vascular smooth muscle cells: the influence of pulmonary hypertension on normal development. J Pathol. 1989 Aug;158(4):311–317. doi: 10.1002/path.1711580408. [DOI] [PubMed] [Google Scholar]
  2. Allen K., Haworth S. G. Human postnatal pulmonary arterial remodeling. Ultrastructural studies of smooth muscle cell and connective tissue maturation. Lab Invest. 1988 Nov;59(5):702–709. [PubMed] [Google Scholar]
  3. Amenta F., Cavallotti C., Ferrante F., Tonelli F. Cholinergic innervation of the human pulmonary circulation. Acta Anat (Basel) 1983;117(1):58–64. doi: 10.1159/000145771. [DOI] [PubMed] [Google Scholar]
  4. Barnes P. J., Cadieux A., Carstairs J. R., Greenberg B., Polak J. M., Rhoden K. Vasoactive intestinal peptide in bovine pulmonary artery: localisation, function and receptor autoradiography. Br J Pharmacol. 1986 Sep;89(1):157–162. doi: 10.1111/j.1476-5381.1986.tb11131.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carstairs J. R., Barnes P. J. Visualization of vasoactive intestinal peptide receptors in human and guinea pig lung. J Pharmacol Exp Ther. 1986 Oct;239(1):249–255. [PubMed] [Google Scholar]
  6. Castairs J. R., Barnes P. J. Autoradiographic mapping of substance P receptors in lung. Eur J Pharmacol. 1986 Aug 15;127(3):295–296. doi: 10.1016/0014-2999(86)90380-8. [DOI] [PubMed] [Google Scholar]
  7. Chamley J. H., Campbell G. R., Burnstock G. Dedifferentiation, redifferentiation and bundle formation of smooth muscle cells in tissue culture: the influence of cell number and nerve fibres. J Embryol Exp Morphol. 1974 Oct;32(2):297–323. [PubMed] [Google Scholar]
  8. D'Orléans-Juste P., Dion S., Drapeau G., Regoli D. Different receptors are involved in the endothelium-mediated relaxation and the smooth muscle contraction of the rabbit pulmonary artery in response to substance P and related neurokinins. Eur J Pharmacol. 1986 Jun 5;125(1):37–44. doi: 10.1016/0014-2999(86)90081-6. [DOI] [PubMed] [Google Scholar]
  9. Dey R. D., Shannon W. A., Jr, Said S. I. Localization of VIP-immunoreactive nerves in airways and pulmonary vessels of dogs, cat, and human subjects. Cell Tissue Res. 1981;220(2):231–238. doi: 10.1007/BF00210505. [DOI] [PubMed] [Google Scholar]
  10. Ekblad E., Edvinsson L., Wahlestedt C., Uddman R., Håkanson R., Sundler F. Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers. Regul Pept. 1984 Apr;8(3):225–235. doi: 10.1016/0167-0115(84)90064-8. [DOI] [PubMed] [Google Scholar]
  11. Geisterfer A. A., Peach M. J., Owens G. K. Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res. 1988 Apr;62(4):749–756. doi: 10.1161/01.res.62.4.749. [DOI] [PubMed] [Google Scholar]
  12. Greenberg B., Rhoden K., Barnes P. J. Relaxant effects of vasoactive intestinal peptide and peptide histidine isoleucine in human and bovine pulmonary arteries. Blood Vessels. 1987;24(1-2):45–50. doi: 10.1159/000158670. [DOI] [PubMed] [Google Scholar]
  13. Gulbenkian S., Wharton J., Hacker G. W., Varndell I. M., Bloom S. R., Polak J. M. Co-localization of neuropeptide tyrosine (NPY) and its C-terminal flanking peptide (C-PON). Peptides. 1985 Nov-Dec;6(6):1237–1243. doi: 10.1016/0196-9781(85)90456-5. [DOI] [PubMed] [Google Scholar]
  14. Gulbenkian S., Wharton J., Polak J. M. The visualisation of cardiovascular innervation in the guinea pig using an antiserum to protein gene product 9.5 (PGP 9.5). J Auton Nerv Syst. 1987 Mar;18(3):235–247. doi: 10.1016/0165-1838(87)90122-6. [DOI] [PubMed] [Google Scholar]
  15. Haworth S. G., Hall S. M., Chew M., Allen K. Thinning of fetal pulmonary arterial wall and postnatal remodelling: ultrastructural studies on the respiratory unit arteries of the pig. Virchows Arch A Pathol Anat Histopathol. 1987;411(2):161–171. doi: 10.1007/BF00712740. [DOI] [PubMed] [Google Scholar]
  16. Haworth S. G., Hislop A. A. Pulmonary vascular development: normal values of peripheral vascular structure. Am J Cardiol. 1983 Sep 1;52(5):578–583. doi: 10.1016/0002-9149(83)90030-9. [DOI] [PubMed] [Google Scholar]
  17. Hua X. Y., Theodorsson-Norheim E., Brodin E., Lundberg J. M., Hökfelt T. Multiple tachykinins (neurokinin A, neuropeptide K and substance P) in capsaicin-sensitive sensory neurons in the guinea-pig. Regul Pept. 1985 Dec;13(1):1–19. doi: 10.1016/0167-0115(85)90082-5. [DOI] [PubMed] [Google Scholar]
  18. Kay J. M. Comparative morphologic features of the pulmonary vasculature in mammals. Am Rev Respir Dis. 1983 Aug;128(2 Pt 2):S53–S57. doi: 10.1164/arrd.1983.128.2P2.S53. [DOI] [PubMed] [Google Scholar]
  19. Keatinge W. R., Torrie C. Action of sympathetic nerves of inner and outer muscle of sheep carotid artery, and effect of pressure on nerve distribution. J Physiol. 1976 Jun;257(3):699–712. doi: 10.1113/jphysiol.1976.sp011393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mak J. C., Barnes P. J. Autoradiographic localization of calcitonin gene-related peptide (CGRP) binding sites in human and guinea pig lung. Peptides. 1988 Sep-Oct;9(5):957–963. doi: 10.1016/0196-9781(88)90073-3. [DOI] [PubMed] [Google Scholar]
  21. Pernow J., Saria A., Lundberg J. M. Mechanisms underlying pre- and postjunctional effects of neuropeptide Y in sympathetic vascular control. Acta Physiol Scand. 1986 Feb;126(2):239–249. doi: 10.1111/j.1748-1716.1986.tb07811.x. [DOI] [PubMed] [Google Scholar]
  22. Sheppard M. N., Polak J. M., Allen J. M., Bloom S. R. Neuropeptide tyrosine (NPY): a newly discovered peptide is present in the mammalian respiratory tract. Thorax. 1984 May;39(5):326–330. doi: 10.1136/thx.39.5.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tanaka D. T., Grunstein M. M. Vasoactive effects of substance P on isolated rabbit pulmonary artery. J Appl Physiol (1985) 1985 Apr;58(4):1291–1297. doi: 10.1152/jappl.1985.58.4.1291. [DOI] [PubMed] [Google Scholar]
  24. Wahlestedt C., Edvinsson L., Ekblad E., Håkanson R. Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction: mode of action. J Pharmacol Exp Ther. 1985 Sep;234(3):735–741. [PubMed] [Google Scholar]
  25. Wharton J., Gulbenkian S., Merighi A., Kuhn D. M., Jahn R., Taylor K. M., Polak J. M. Immunohistochemical and ultrastructural localisation of peptide-containing nerves and myocardial cells in the human atrial appendage. Cell Tissue Res. 1988 Oct;254(1):155–166. doi: 10.1007/BF00220029. [DOI] [PubMed] [Google Scholar]
  26. Wharton J., Gulbenkian S., Mulderry P. K., Ghatei M. A., McGregor G. P., Bloom S. R., Polak J. M. Capsaicin induces a depletion of calcitonin gene-related peptide (CGRP)-immunoreactive nerves in the cardiovascular system of the guinea pig and rat. J Auton Nerv Syst. 1986 Aug;16(4):289–309. doi: 10.1016/0165-1838(86)90035-4. [DOI] [PubMed] [Google Scholar]
  27. Wharton J., Haworth S. G., Polak J. M. Postnatal development of the innervation and paraganglia in the porcine pulmonary arterial bed. J Pathol. 1988 Jan;154(1):19–27. doi: 10.1002/path.1711540104. [DOI] [PubMed] [Google Scholar]
  28. Wiedenmann B., Franke W. W. Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles. Cell. 1985 Jul;41(3):1017–1028. doi: 10.1016/s0092-8674(85)80082-9. [DOI] [PubMed] [Google Scholar]

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