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. 1993 Apr;48(4):324–329. doi: 10.1136/thx.48.4.324

Comparative nasal effects of bradykinin and histamine: influence on nasal airways resistance and plasma protein exudation.

K Rajakulasingam 1, R Polosa 1, L C Lau 1, M K Church 1, S T Holgate 1, P H Howarth 1
PMCID: PMC464426  PMID: 8511729

Abstract

BACKGROUND--Bradykinin may contribute to the pathogenesis of allergic rhinitis. Like histamine, nasal challenge with bradykinin induces rhinorrhoea, nasal blockage, and plasma protein leakage. Their comparative nasal potencies have not, however, been fully elucidated. METHODS--Three double blind, randomised, placebo controlled and cross-over studies were undertaken to compare objectively the nasal effects of bradykinin, histamine, and vehicle. RESULTS--Both bradykinin and histamine produced dose dependent increases in nasal airways resistance (NAR). There was no significant difference in the effects of bradykinin and histamine on NAR at any dose level. On a molar basis, however, bradykinin was 6.98 times more potent than histamine in inducing a 50% increase in NAR. Nasal challenge with bradykinin and histamine also induced significant rhinorrhoea compared with vehicle. The amount of rhinorrhoea induced by histamine was significantly greater than that induced by bradykinin at any dose level. Bradykinin and histamine induced dose dependent nasal pain and nasal itch respectively. When administered as single doses both bradykinin (1.9 mumol) and histamine (1.9 mumol) induced significant rhinorrhoea compared with the vehicle. The volume of rhinorrhoea secretions induced by histamine was 29% greater than that induced by bradykinin. In contrast, although NAR was increased significantly more by histamine than by the vehicle, the effect of bradykinin on NAR was significantly greater than histamine and vehicle in both magnitude and duration of effect. The incremental effect of bradykinin on lavage albumin levels was also significantly greater than both histamine and vehicle. CONCLUSIONS--This study shows that the nasal vascular effects of histamine are less prominent than its actions on rhinorrhoea, and that the greater obstructive effect of bradykinin than histamine on NAR may contribute to the relative lack of efficacy of H1 antihistamines on nasal blockage in clinical disease.

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Selected References

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  1. Baraniuk J. N., Lundgren J. D., Mizoguchi H., Peden D., Gawin A., Merida M., Shelhamer J. H., Kaliner M. A. Bradykinin and respiratory mucous membranes. Analysis of bradykinin binding site distribution and secretory responses in vitro and in vivo. Am Rev Respir Dis. 1990 Mar;141(3):706–714. doi: 10.1164/ajrccm/141.3.706. [DOI] [PubMed] [Google Scholar]
  2. Borum P., Grønborg H., Brofeldt S., Mygind N. Nasal reactivity in rhinitis. Eur J Respir Dis Suppl. 1983;128(Pt 1):65–71. [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  4. Corrado O. J., Gould C. A., Kassab J. Y., Davies R. J. Nasal response of rhinitic and non-rhinitic subjects to histamine and methacholine: a comparative study. Thorax. 1986 Nov;41(11):863–868. doi: 10.1136/thx.41.11.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Doyle W. J., Boehm S., Skoner D. P. Physiologic responses to intranasal dose-response challenges with histamine, methacholine, bradykinin, and prostaglandin in adult volunteers with and without nasal allergy. J Allergy Clin Immunol. 1990 Dec;86(6 Pt 1):924–935. doi: 10.1016/s0091-6749(05)80156-3. [DOI] [PubMed] [Google Scholar]
  6. Holmberg K., Bake B., Pipkorn U. Vascular effects of topically applied bradykinin on the human nasal mucosa. Eur J Pharmacol. 1990 Jan 3;175(1):35–41. doi: 10.1016/0014-2999(90)90149-z. [DOI] [PubMed] [Google Scholar]
  7. Howarth P. H. Allergic rhinitis: a rational choice of treatment. Respir Med. 1989 May;83(3):179–188. doi: 10.1016/s0954-6111(89)80029-0. [DOI] [PubMed] [Google Scholar]
  8. Howarth P. H., Wilson S., Lau L., Rajakulasingam K. The nasal mast cell and rhinitis. Clin Exp Allergy. 1991 May;21 (Suppl 2):3–8. doi: 10.1111/j.1365-2222.1991.tb01751.x. [DOI] [PubMed] [Google Scholar]
  9. Marceau F., Lussier A., Regoli D., Giroud J. P. Pharmacology of kinins: their relevance to tissue injury and inflammation. Gen Pharmacol. 1983;14(2):209–229. doi: 10.1016/0306-3623(83)90001-0. [DOI] [PubMed] [Google Scholar]
  10. Naclerio R. M., Meier H. L., Kagey-Sobotka A., Adkinson N. F., Jr, Meyers D. A., Norman P. S., Lichtenstein L. M. Mediator release after nasal airway challenge with allergen. Am Rev Respir Dis. 1983 Oct;128(4):597–602. doi: 10.1164/arrd.1983.128.4.597. [DOI] [PubMed] [Google Scholar]
  11. Naclerio R. M., Proud D., Lichtenstein L. M., Kagey-Sobotka A., Hendley J. O., Sorrentino J., Gwaltney J. M. Kinins are generated during experimental rhinovirus colds. J Infect Dis. 1988 Jan;157(1):133–142. doi: 10.1093/infdis/157.1.133. [DOI] [PubMed] [Google Scholar]
  12. Naclerio R. M., Proud D., Peters S. P., Silber G., Kagey-Sobotka A., Adkinson N. F., Jr, Lichtenstein L. M. Inflammatory mediators in nasal secretions during induced rhinitis. Clin Allergy. 1986 Mar;16(2):101–110. doi: 10.1111/j.1365-2222.1986.tb00753.x. [DOI] [PubMed] [Google Scholar]
  13. Naclerio R. M., Proud D., Togias A. G., Adkinson N. F., Jr, Meyers D. A., Kagey-Sobotka A., Plaut M., Norman P. S., Lichtenstein L. M. Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med. 1985 Jul 11;313(2):65–70. doi: 10.1056/NEJM198507113130201. [DOI] [PubMed] [Google Scholar]
  14. Proud D., Naclerio R. M., Gwaltney J. M., Hendley J. O. Kinins are generated in nasal secretions during natural rhinovirus colds. J Infect Dis. 1990 Jan;161(1):120–123. doi: 10.1093/infdis/161.1.120. [DOI] [PubMed] [Google Scholar]
  15. Proud D., Reynolds C. J., Lacapra S., Kagey-Sobotka A., Lichtenstein L. M., Naclerio R. M. Nasal provocation with bradykinin induces symptoms of rhinitis and a sore throat. Am Rev Respir Dis. 1988 Mar;137(3):613–616. doi: 10.1164/ajrccm/137.3.613. [DOI] [PubMed] [Google Scholar]
  16. Proud D., Togias A., Naclerio R. M., Crush S. A., Norman P. S., Lichtenstein L. M. Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen. J Clin Invest. 1983 Nov;72(5):1678–1685. doi: 10.1172/JCI111127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rajakulasingam K., Polosa R., Holgate S. T., Howarth P. H. Comparative nasal effects of bradykinin, kallidin and [Des-Arg9]-bradykinin in atopic rhinitic and normal volunteers. J Physiol. 1991 Jun;437:577–587. doi: 10.1113/jphysiol.1991.sp018612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rajakulasingam K., Polosa R., Lau L. C., Church M. K., Holgate S. T., Howarth P. H. The influence of terfenadine and ipratropium bromide alone and in combination on bradykinin-induced nasal symptoms and plasma protein leakage. Clin Exp Allergy. 1992 Jul;22(7):717–723. doi: 10.1111/j.1365-2222.1992.tb00196.x. [DOI] [PubMed] [Google Scholar]
  19. Raphael G. D., Meredith S. D., Baraniuk J. N., Druce H. M., Banks S. M., Kaliner M. A. The pathophysiology of rhinitis. II. Assessment of the sources of protein in histamine-induced nasal secretions. Am Rev Respir Dis. 1989 Mar;139(3):791–800. doi: 10.1164/ajrccm/139.3.791. [DOI] [PubMed] [Google Scholar]
  20. Svensson C., Andersson M., Persson C. G., Venge P., Alkner U., Pipkorn U. Albumin, bradykinins, and eosinophil cationic protein on the nasal mucosal surface in patients with hay fever during natural allergen exposure. J Allergy Clin Immunol. 1990 May;85(5):828–833. doi: 10.1016/0091-6749(90)90064-b. [DOI] [PubMed] [Google Scholar]
  21. Svensson C., Baumgarten C. R., Pipkorn U., Alkner U., Persson C. G. Reversibility and reproducibility of histamine induced plasma leakage in nasal airways. Thorax. 1989 Jan;44(1):13–18. doi: 10.1136/thx.44.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Townley R. J., Hopp R. J. Inhalation methods for the study of airway responsiveness. J Allergy Clin Immunol. 1987 Aug;80(2):111–124. doi: 10.1016/0091-6749(87)90116-3. [DOI] [PubMed] [Google Scholar]
  23. Weeke B. Rocket immunoelectrophoresis. Scand J Immunol Suppl. 1973;1:37–46. doi: 10.1111/j.1365-3083.1973.tb03777.x. [DOI] [PubMed] [Google Scholar]

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