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. 1993 Oct;110(2):657–664. doi: 10.1111/j.1476-5381.1993.tb13862.x

Bradykinin-induced airflow obstruction and airway plasma exudation: effects of drugs that inhibit acetylcholine, thromboxane A2 or leukotrienes.

I Kawikova 1, H Arakawa 1, C G Löfdahl 1, B E Skoogh 1, J Lötvall 1
PMCID: PMC2175931  PMID: 8242239

Abstract

1. The mechanisms behind bradykinin-induced effects in the airways are considered to be largely indirect. The role of cholinergic nerves and eicosanoids, and their relationship in these mechanisms were investigated in guinea-pigs. 2. The role of cholinergic nerves was studied in animals given atropine (1 mg kg-1, i.v.), hexamethonium (2 mg kg-1, i.v.), or vagotomized. To study the role of eicosanoids, animals were pretreated with a thromboxane A2 (TxA2) receptor antagonist (ICI 192,605; 10(-6) mol kg-1, i.v.) or with a leukotriene (LT) receptor C4/D4/E4 antagonist (ICI 198,615; 10(-6) mol kg-1, i.v.). 3. After pretreatment with a drug, bradykinin (150 nmol) was instilled into the tracheal lumen. We measured both airway insufflation pressure (Pi), to assess airway narrowing, and the content of Evans blue dye in airway tissue, to assess plasma exudation. 4. Bradykinin instillation into the trachea caused an increase in Pi and extravasation of Evans blue dye. The increase in Pi was significantly attenuated by atropine or the TxA2 receptor antagonist, but not by hexamethonium, vagotomy or the LT receptor antagonist. 5. The bradykinin-induced exudation of Evans blue dye was significantly attenuated in the intrapulmonary airways by the TxA2 receptor antagonist, but not by atropine, hexamethonium, cervical vagotomy or the LT receptor antagonist. 6. A thromboxane-mimetic U-46619 (20 nmol kg-1, i.v. or 10 nmol intratracheally), caused both an increase in Pi and extravasation of Evans blue dye at all airway levels. Atropine pretreatment slightly attenuated the peak Pi after the intratracheal administration of U-46619, but not after i.v. administration.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Abe K., Watanabe N., Kumagai N., Mouri T., Seki T., Yoshinaga K. Circulating kinin in patients with bronchial asthma. Experientia. 1967 Aug 15;23(8):626–627. doi: 10.1007/BF02144161. [DOI] [PubMed] [Google Scholar]
  2. Arakawa H., Kawikova I., Löfdahl C. G., Lötvall J. Bradykinin-induced airway responses in guinea pig: effects of inhibition of cyclooxygenase and thromboxane synthetase. Eur J Pharmacol. 1992 Dec 15;229(2-3):131–136. doi: 10.1016/0014-2999(92)90546-g. [DOI] [PubMed] [Google Scholar]
  3. BHOOLA K. D., COLLIER H. O., SCHACHTER M., SHORLEY P. G. Actions of some peptides on bronchial muscle. Br J Pharmacol Chemother. 1962 Aug;19:190–197. doi: 10.1111/j.1476-5381.1962.tb01439.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barnes P. J., Chung K. F., Page C. P. Inflammatory mediators and asthma. Pharmacol Rev. 1988 Mar;40(1):49–84. [PubMed] [Google Scholar]
  5. COLLIER H. O., HOLGATE J. A., SCHACHTER M., SHORLEY P. G. The bronchoconstrictor action of bradykinin in the guinea-pig. Br J Pharmacol Chemother. 1960 Jun;15:290–297. doi: 10.1111/j.1476-5381.1960.tb01247.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Christiansen S. C., Proud D., Cochrane C. G. Detection of tissue kallikrein in the bronchoalveolar lavage fluid of asthmatic subjects. J Clin Invest. 1987 Jan;79(1):188–197. doi: 10.1172/JCI112782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chung K. F., Evans T. W., Graf P. D., Nadel J. A. Modulation of cholinergic neurotransmission in canine airways by thromboxane mimetic U46619. Eur J Pharmacol. 1985 Nov 19;117(3):373–375. doi: 10.1016/0014-2999(85)90012-3. [DOI] [PubMed] [Google Scholar]
  8. Dusser D. J., Nadel J. A., Sekizawa K., Graf P. D., Borson D. B. Neutral endopeptidase and angiotensin converting enzyme inhibitors potentiate kinin-induced contraction of ferret trachea. J Pharmacol Exp Ther. 1988 Feb;244(2):531–536. [PubMed] [Google Scholar]
  9. 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]
  10. Farmer S. G., Burch R. M., Meeker S. A., Wilkins D. E. Evidence for a pulmonary B3 bradykinin receptor. Mol Pharmacol. 1989 Jul;36(1):1–8. [PubMed] [Google Scholar]
  11. Farmer S. G., Ensor J. E., Burch R. M. Evidence that cultured airway smooth muscle cells contain bradykinin B2 and B3 receptors. Am J Respir Cell Mol Biol. 1991 Mar;4(3):273–277. doi: 10.1165/ajrcmb/4.3.273. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Hey J. A., del Prado M., Chapman R. W. Activation of a novel medullary pathway elicits a vagal, cholinergic bronchoconstriction in guinea-pigs. Pulm Pharmacol. 1990;3(1):53–54. doi: 10.1016/0952-0600(90)90010-g. [DOI] [PubMed] [Google Scholar]
  14. Ichinose M., Belvisi M. G., Barnes P. J. Bradykinin-induced bronchoconstriction in guinea pig in vivo: role of neural mechanisms. J Pharmacol Exp Ther. 1990 May;253(2):594–599. [PubMed] [Google Scholar]
  15. Kaufman M. P., Coleridge H. M., Coleridge J. C., Baker D. G. Bradykinin stimulates afferent vagal C-fibers in intrapulmonary airways of dogs. J Appl Physiol Respir Environ Exerc Physiol. 1980 Mar;48(3):511–517. doi: 10.1152/jappl.1980.48.3.511. [DOI] [PubMed] [Google Scholar]
  16. Lötvall J. O., Lemen R. J., Hui K. P., Barnes P. J., Chung K. F. Airflow obstruction after substance P aerosol: contribution of airway and pulmonary edema. J Appl Physiol (1985) 1990 Oct;69(4):1473–1478. doi: 10.1152/jappl.1990.69.4.1473. [DOI] [PubMed] [Google Scholar]
  17. Lötvall J. O., Tokuyama K., Barnes P. J., Chung K. F. Bradykinin-induced airway microvascular leakage is potentiated by captopril and phosphoramidon. Eur J Pharmacol. 1991 Aug 6;200(2-3):211–217. doi: 10.1016/0014-2999(91)90574-a. [DOI] [PubMed] [Google Scholar]
  18. Lötvall J., Elwood W., Tokuyama K., Sakamoto T., Barnes P. J., Chung K. F. A thromboxane mimetic, U-46619, produces plasma exudation in airways of the guinea pig. J Appl Physiol (1985) 1992 Jun;72(6):2415–2419. doi: 10.1152/jappl.1992.72.6.2415. [DOI] [PubMed] [Google Scholar]
  19. Piper P. J., Collier H. O. Release of catecholamines in the guinea-pig by substances involved in anaphylaxis. Nature. 1967 Feb 25;213(5078):838–840. doi: 10.1038/213838a0. [DOI] [PubMed] [Google Scholar]
  20. Polosa R., Phillips G. D., Lai C. K., Holgate S. T. Contribution of histamine and prostanoids to bronchoconstriction provoked by inhaled bradykinin in atopic asthma. Allergy. 1990 Apr;45(3):174–182. doi: 10.1111/j.1398-9995.1990.tb00480.x. [DOI] [PubMed] [Google Scholar]
  21. Regoli D., Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980 Mar;32(1):1–46. [PubMed] [Google Scholar]
  22. Rogers D. F., Boschetto P., Barnes P. J. Plasma exudation. Correlation between Evans blue dye and radiolabeled albumin in guinea pig airways in vivo. J Pharmacol Methods. 1989 Jul;21(4):309–315. doi: 10.1016/0160-5402(89)90068-5. [DOI] [PubMed] [Google Scholar]
  23. 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]
  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. Saria A., Martling C. R., Yan Z., Theodorsson-Norheim E., Gamse R., Lundberg J. M. Release of multiple tachykinins from capsaicin-sensitive sensory nerves in the lung by bradykinin, histamine, dimethylphenyl piperazinium, and vagal nerve stimulation. Am Rev Respir Dis. 1988 Jun;137(6):1330–1335. doi: 10.1164/ajrccm/137.6.1330. [DOI] [PubMed] [Google Scholar]
  26. Shirley J. T., Cheng J. B. Competition of leukotrienes and ICI-198,615 for [3H]LTD4 binding sites in guinea pig lung membranes suggests the involvement of two LTD4 receptor subtypes. J Pharmacol Exp Ther. 1991 Aug;258(2):531–536. [PubMed] [Google Scholar]
  27. Simonsson B. G., Skoogh B. E., Bergh N. P., Andersson R., Svedmyr N. In vivo and in vitro effect of bradykinin on bronchial motor tone in normal subjects and patients with airways obstruction. Respiration. 1973;30(4):378–388. doi: 10.1159/000193051. [DOI] [PubMed] [Google Scholar]
  28. Thijssen H. H., Baars L. G., Vervoort-Peters H. T. Vitamin K 2,3-epoxide reductase: the basis for stereoselectivity of 4-hydroxycoumarin anticoagulant activity. Br J Pharmacol. 1988 Nov;95(3):675–682. doi: 10.1111/j.1476-5381.1988.tb11692.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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