Skip to main content
Log in

Lack of a role for bradykinin in inhaled sodium metabisulphite-induced airway microvascular leakage in guinea pigs

  • Published:
InflammoPharmacology Aims and scope Submit manuscript

Abstract

We have investigated the role of bradykinin in airway microvascular leakage and bronchoconstriction induced by inhaled sodium metabisulphite (MBS) in guinea pigs. A selective bradykinin B2 receptor antagonist, HOE 140 (D-Arg[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin), was used because this drug has been shown to abolish the airway responses induced by bradykinin. Lung resistance (RL) was measured for 6 min after challenge with MBS, followed by measurement of extravasation of Evans Blue dye into airway tissues, used as an index of plasma exudation. Aerosolized MBS (40 and 80 mmol/L, 30 breaths) induced a significant increase in RL and leakage of dye in the trachea, main bronchi and intrapulmonary airways, whereas 20 mmol/L MBS caused these responses except for the dye leakage in the trachea and main bronchi. HOE 140 (100 nmol/kg iv) had no effect against these airway responses. We conclude that bradykinin-mediated mechanisms do not play a significant role in the acute airway effects induced by inhaled MBS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Nichol GM, Nix A, Chung KF, Barnes PJ. Characterisation of bronchoconstrictor responses to sodium metabisulfite aerosol in atopic subjects with and without asthma. Thorax. 1989;44:1009–14.

    Article  PubMed  CAS  Google Scholar 

  2. Dixon CMS, Ind PW. Inhaled sodium metabisulfite induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate. Br J Clin Pharmacol. 1990;30:371–6.

    PubMed  CAS  Google Scholar 

  3. Lotvall JO, Skoogh B-E, Lemen RJ, Elwood W, Barnes PJ, Chung KF. Bronchoconstriction induced by inhaled sodium metabisulfite in the guinea pig. Am Rev Respir Dis. 1990;142:1390–5.

    PubMed  CAS  Google Scholar 

  4. Sakamoto T, Elwood W, Barnes PJ, Chung KF. Pharmacological modulation of inhaled sodium metabisulphite-induced airway microvascular leakage and bronchoconstriction in the guinea pig. Br J Pharmacol. 1992;107:481–7.

    PubMed  CAS  Google Scholar 

  5. Collier HOJ, Holgate JA, Schachter M, Shorley PG. The bronchoconstrictor action of bradykinin in the guinea-pig. Br J Pharmacol. 1960;15:290–7.

    CAS  Google Scholar 

  6. Saria A, Lundberg JM, Skofitsch G, Lembeck F. Vascular protein leakage in various tissues induced by substance P, capsaicin, bradykinin, serotonin, histamine and antigen challenge. Naunyn-Schmiedeberg's Arch Pharmacol. 1983;324:212–18.

    Article  CAS  Google Scholar 

  7. Rogers DF, Dijk S, Barnes PJ. Bradykinin-induced plasma exudation in guinea-pig airways: involvement of platelet activating factor. Br J Pharmacol. 1990;101:739–45.

    PubMed  CAS  Google Scholar 

  8. Sakamoto T, Barnes PJ, Chung KF. Bradykinin-induced bronchoconstriction in guinea pig in vivo: role of neural mechanisms. J Pharmacol Exp Ther. 1990;253:594–9.

    Google Scholar 

  9. Sakamoto T, Barnes PJ, Chung KF. Effect of CP-96,345, a non-peptide NK1 receptor antagonist, against substance P-, bradykinin- and allergen-induced airway microvascular leakage and bronchoconstriction in the guinea pig. Eur J Pharmacol. 1993;231:31–8.

    Article  PubMed  CAS  Google Scholar 

  10. Sakamoto T, Tsukagoshi H, Barnes PJ, Chung KF. Involvement of tachykinin receptors (NK1 and NK2) in sodium metabisulfite-induced airway effects. Am J Respir Crit Care Med. 1994;149:387–91.

    PubMed  CAS  Google Scholar 

  11. Proud D, Kaplan AP. Kinin formation: mechanisms and role in inflammatory disorders. Ann Rev Immunol. 1988;6:49–83.

    Article  CAS  Google Scholar 

  12. Mansour E, Ahmed A, Cortes A, Caplan J, Burch RM, Abraham WM. Mechanisms of metabisulfite-induced bronchoconstriction: evidence for bradykinin B2-receptor stimulation. J Appl Physiol. 1992;72:1831–7.

    PubMed  CAS  Google Scholar 

  13. Lembeck F, Griesbacher T, Eckhardt M, Henke S, Breipohl G, Knolle J. New, long-acting, potent bradykinin antagonists. Br J Pharmacol. 1991;102:297–304.

    PubMed  CAS  Google Scholar 

  14. Hock FJ, Wirth K, Albus U et al. HOE 140 a new potent and long acting bradykinin-antagonist: in vitro studies. Br J Pharmacol. 1991;102:769–73.

    PubMed  CAS  Google Scholar 

  15. Wirth K, Hock FJ, Albus U et al. HOE 140 a new potent long acting bradykinin-antagonist: in vivo studies. Br J Pharmacol. 1991;102:774–7.

    PubMed  CAS  Google Scholar 

  16. Sakamoto T, Elwood W, Barnes PJ, Chung KF. Effect of HOE 140, a new bradykinin receptor antagonist, on bradykinin- and platelet activating factor-induced bronchoconstriction and airway microvascular leakage in guinea pig. Eur J Pharmacol. 1992;213:367–73.

    Article  PubMed  CAS  Google Scholar 

  17. Sakamoto T, Sun J, Barnes PJ, Chung KF. Effect of a bradykinin receptor antagonist, HOE 140, against bradykinin- and vagal stimulation-induced airway responses in the guinea pig. Eur J Pharmacol. 1994;251:137–42.

    Article  PubMed  CAS  Google Scholar 

  18. von Neergaad K, Wirz K. Die Messung der Stromungswiderstande in den Atemwegen des Menschen, insbesondere bei Asthma und Emphysem. Z Klin Med. 1927;105:51–82.

    Google Scholar 

  19. Rogers DF, Boschetto P, Barnes PJ. Plasma exudation: correlation between Evans Blue dye and radiolabelled albumin in guinea-pig airways in vivo. J Pharmacol Meth. 1989;21:309–15.

    Article  CAS  Google Scholar 

  20. Chung KF, Rogers DF, Barnes PJ, Evans TW. The role of increased airway microvascular permeability and plasma exudation in asthma. Eur Respir J. 1990;3:329–37.

    PubMed  CAS  Google Scholar 

  21. Bertrand C, Nadel JA, Yamawaki I, Geppetti P. Role of kinins in the vascular extravasation evoked by antigen and mediated by tachykinins in guinea pig trachea. J Immunol. 1993;151:4902–7.

    PubMed  CAS  Google Scholar 

  22. Ichinose M, Belvisi M, Barnes PJ. Bradykinin-induced bronchoconstriction in guinea pig in vivo: role of neural mechanisms. J Pharmacol Exp Ther. 1990;253:594–9.

    PubMed  CAS  Google Scholar 

  23. Farmer SG, Burch RM, Meeker SA, Wilkins DE. Evidence for a pulmonary B3 bradykinin receptor. Mol Pharmacol. 1989;36:1–8.

    PubMed  CAS  Google Scholar 

  24. Nichol GM, Parsons GH, Barnes PJ, Chung KF. Metabisulfite aerosol increases bronchial blood flow despite anticholinergic, furosemide, nedocromil, or antihistamine pretreatment. Am Rev Respir Dis. 1990;141 (Suppl):360.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakamoto, T., Chung, K.F. Lack of a role for bradykinin in inhaled sodium metabisulphite-induced airway microvascular leakage in guinea pigs. Inflammopharmacology 4, 323–330 (1996). https://doi.org/10.1007/BF02755785

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02755785

Keywords

Navigation