Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Sep;104(1):128–132. doi: 10.1111/j.1476-5381.1991.tb12396.x

Quantitative assessment of increased airway microvascular permeability to 125I-labelled plasma fibrinogen induced by platelet activating factor and bradykinin.

K E Pedersen 1, P J Rigby 1, R G Goldie 1
PMCID: PMC1908305  PMID: 1664758

Abstract

1. We have used 125I-labelled fibrinogen (I-FN) in experiments monitoring plasma extravasation from vessels within guinea-pig trachea and peripheral lung tissue in response to platelet activating factor (PAF) and bradykinin (BK). Retained tissue radioactivity derived from I-FN was detected by direct measurement and by autoradiography. 2. Both PAF and BK caused concentration-dependent increases in radioactivity in trachea and peripheral lung, with PAF being approximately 1000 times more potent than BK at both sites. On a wet weight basis, mean tracheal leakage responses to PAF and BK were approximately 6 times and 2 times greater respectively than those in peripheral lung. Furthermore, in trachea, the maximal response to PAF was nearly twice that to BK, although they were approximately equiactive in peripheral lung. The dipeptidyl carboxypeptidase inhibitor, enalapril (1 mg kg-1, i.v.), increased the potency of BK by approximately 40 fold. 3. In trachea, PAF (50 ng kg-1, i.v.)-induced leakage was selectively inhibited by the PAF receptor antagonist, WEB 2086 (5-50 micrograms kg-1), while responses to BK (50 micrograms kg-1, i.v.) were selectively inhibited by the BK2 receptor antagonist NPC 349 (0.5-1 mg kg-1). Neither PAF nor BK-induced leakage were significantly altered by pretreatment with the histamine H1-receptor antagonists mepyramine (10 micrograms kg-1) or ketotifen (50 micrograms kg-1) or the leukotriene receptor antagonist SKF 104353. These data indicate that both agonists caused direct, specific receptor operated increases in tracheal vascular permeability to plasma macromolecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
128

Images in this article

Selected References

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

  1. Barnes P. J., Chung K. F., Page C. P. Inflammatory mediators and asthma. Pharmacol Rev. 1988 Mar;40(1):49–84. [PubMed] [Google Scholar]
  2. Barnes P. J. Inflammatory mediator receptors and asthma. Am Rev Respir Dis. 1987 Jun;135(6 Pt 2):S26–S31. doi: 10.1164/arrd.1987.135.6P2.S26. [DOI] [PubMed] [Google Scholar]
  3. Belvisi M. G., Rogers D. F., Barnes P. J. Neurogenic plasma extravasation: inhibition by morphine in guinea pig airways in vivo. J Appl Physiol (1985) 1989 Jan;66(1):268–272. doi: 10.1152/jappl.1989.66.1.268. [DOI] [PubMed] [Google Scholar]
  4. Bertram J. F., Goldie R. G., Papadimitriou J. M., Paterson J. W. Correlations between pharmacological responses and structure of human lung parenchyma strips. Br J Pharmacol. 1983 Sep;80(1):107–114. doi: 10.1111/j.1476-5381.1983.tb11055.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boschetto P., Roberts N. M., Rogers D. F., Barnes P. J. Effect of antiasthma drugs on microvascular leakage in guinea pig airways. Am Rev Respir Dis. 1989 Feb;139(2):416–421. doi: 10.1164/ajrccm/139.2.416. [DOI] [PubMed] [Google Scholar]
  6. Cuss F. M., Dixon C. M., Barnes P. J. Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man. Lancet. 1986 Jul 26;2(8500):189–192. doi: 10.1016/s0140-6736(86)92489-x. [DOI] [PubMed] [Google Scholar]
  7. DUNNILL M. S. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol. 1960 Jan;13:27–33. doi: 10.1136/jcp.13.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Erjefält I., Persson C. G. Inflammatory passage of plasma macromolecules into airway wall and lumen. Pulm Pharmacol. 1989;2(2):93–102. doi: 10.1016/0952-0600(89)90030-6. [DOI] [PubMed] [Google Scholar]
  9. Evans T. W., Chung K. F., Rogers D. F., Barnes P. J. Effect of platelet-activating factor on airway vascular permeability: possible mechanisms. J Appl Physiol (1985) 1987 Aug;63(2):479–484. doi: 10.1152/jappl.1987.63.2.479. [DOI] [PubMed] [Google Scholar]
  10. Evans T. W., Dent G., Rogers D. F., Aursudkij B., Chung K. F., Barnes P. J. Effect of a Paf antagonist, WEB 2086, on airway microvascular leakage in the guinea-pig and platelet aggregation in man. Br J Pharmacol. 1988 May;94(1):164–168. doi: 10.1111/j.1476-5381.1988.tb11511.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fuller R. W., Dixon C. M., Cuss F. M., Barnes P. J. Bradykinin-induced bronchoconstriction in humans. Mode of action. Am Rev Respir Dis. 1987 Jan;135(1):176–180. doi: 10.1164/arrd.1987.135.1.176. [DOI] [PubMed] [Google Scholar]
  12. Goldie R. G., Pedersen K. E., Rigby P. J., Paterson J. W. PAF receptors in guinea-pig and human lung. Agents Actions Suppl. 1990;31:243–246. doi: 10.1007/978-3-0348-7379-6_32. [DOI] [PubMed] [Google Scholar]
  13. Henry P. J., Rigby P. J., Goldie R. G. Distribution of beta 1- and beta 2-adrenoceptors in mouse trachea and lung: a quantitative autoradiographic study. Br J Pharmacol. 1990 Jan;99(1):136–144. doi: 10.1111/j.1476-5381.1990.tb14667.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Henry P. J., Rigby P. J., Self G. J., Preuss J. M., Goldie R. G. Relationship between endothelin-1 binding site densities and constrictor activities in human and animal airway smooth muscle. Br J Pharmacol. 1990 Aug;100(4):786–792. doi: 10.1111/j.1476-5381.1990.tb14093.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ichinose M., Barnes P. J. Bradykinin-induced airway microvascular leakage and bronchoconstriction are mediated via a bradykinin B2 receptor. Am Rev Respir Dis. 1990 Nov;142(5):1104–1107. doi: 10.1164/ajrccm/142.5.1104. [DOI] [PubMed] [Google Scholar]
  16. Jin L. S., Seeds E., Page C. P., Schachter M. Inhibition of bradykinin-induced bronchoconstriction in the guinea-pig by a synthetic B2 receptor antagonist. Br J Pharmacol. 1989 Jun;97(2):598–602. doi: 10.1111/j.1476-5381.1989.tb11991.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. O'Donnell S. R., Barnett C. J. Microvascular leakage to platelet activating factor in guinea-pig trachea and bronchi. Eur J Pharmacol. 1987 Jun 26;138(3):385–396. doi: 10.1016/0014-2999(87)90477-8. [DOI] [PubMed] [Google Scholar]
  18. Persson C. G., Erjefält I. Terbutaline and adrenaline inhibit leakage of fluid and protein in guinea-pig lung. Eur J Pharmacol. 1979 Apr 15;55(2):199–201. doi: 10.1016/0014-2999(79)90392-3. [DOI] [PubMed] [Google Scholar]
  19. Persson C. G. Leakage of macromolecules from the tracheobronchial microcirculation. Am Rev Respir Dis. 1987 Jun;135(6 Pt 2):S71–S75. doi: 10.1164/arrd.1987.135.6P2.S71. [DOI] [PubMed] [Google Scholar]
  20. Persson C. G. Role of plasma exudation in asthmatic airways. Lancet. 1986 Nov 15;2(8516):1126–1129. doi: 10.1016/s0140-6736(86)90533-7. [DOI] [PubMed] [Google Scholar]
  21. Rogers D. F., Dijk S., Barnes P. J. Bradykinin-induced plasma exudation in guinea-pig airways: involvement of platelet activating factor. Br J Pharmacol. 1990 Nov;101(3):739–745. doi: 10.1111/j.1476-5381.1990.tb14150.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ryan G. B., Majno G. Acute inflammation. A review. Am J Pathol. 1977 Jan;86(1):183–276. [PMC free article] [PubMed] [Google Scholar]
  23. Saldeen T. Quantiative determination of intravascular coagulation in the lungs of experimental animals. Scand J Haematol. 1969;6(3):205–215. doi: 10.1111/j.1600-0609.1969.tb01827.x. [DOI] [PubMed] [Google Scholar]
  24. Saria A., Lundberg J. M., Skofitsch G., Lembeck F. Vascular protein linkage in various tissue induced by substance P, capsaicin, bradykinin, serotonin, histamine and by antigen challenge. Naunyn Schmiedebergs Arch Pharmacol. 1983 Nov;324(3):212–218. doi: 10.1007/BF00503897. [DOI] [PubMed] [Google Scholar]
  25. Sirois M. G., Plante G. E., Braquet P., Sirois P. Role of eicosanoids in PAF-induced increases of the vascular permeability in rat airways. Br J Pharmacol. 1990 Dec;101(4):896–900. doi: 10.1111/j.1476-5381.1990.tb14177.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES