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The influence of cyclooxygenase inhibition on the loss of bronchoconstrictor response to repeated bradykinin challenge in asthma.
Eur Respir J 1990; 3(8):914-21ER

Abstract

Bradykinin is a naturally occurring nonapeptide which may contribute to the pathogenesis of bronchial asthma. When inhaled by asthmatic subjects it is a potent bronchoconstrictor, but with repeated challenge airways responsiveness to the peptide decreases markedly. In vitro studies suggest that loss of bradykinin responsiveness may be due to the secondary generation of relaxant prostanoids. We have used the potent cyclooxygenase inhibitor flurbiprofen to investigate the potential role of prostanoid generation in bradykinin tachyphylaxis in eight asthmatic patients. The effects of oral flurbiprofen (150 mg) and matched placebo were observed on two consecutive dose response studies with inhaled bradykinin and histamine in a double-blind, randomized study. Venous blood was taken to measure the serum concentration of thromboxane B2 (TxB2) as a check on the extent of cyclooxygenase blockade achieved by flurbiprofen. Following recovery from the first challenge with bradykinin, the asthmatic airways showed a reduced response to a second challenge with this nonapeptide, the provocative concentration producing a 20% fall from baseline (PC20) increasing from 0.07 to 0.42 mg.ml-1 (p less than 0.01). The airway response to inhaled histamine after the second bradykinin challenge was not significantly changed. In the presence of demonstrable cyclooxygenase inhibition, flurbiprofen failed to prevent the development of reduced responsiveness to bradykinin observed on the second challenge, the PC20 increasing from 0.10 to 0.48 mg.ml-1 (p less than 0.01). This study demonstrates that repeated exposure to inhaled bradykinin results in loss of the bronchoconstrictor response which appears specific for this agonist and not secondary to the increased generation of protective prostanoids.

Authors+Show Affiliations

Dept of Immunopharmacology, Southampton University and General Hospital, Hampshire, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

2127257

Citation

Polosa, R, et al. "The Influence of Cyclooxygenase Inhibition On the Loss of Bronchoconstrictor Response to Repeated Bradykinin Challenge in Asthma." The European Respiratory Journal, vol. 3, no. 8, 1990, pp. 914-21.
Polosa R, Lai CK, Robinson C, et al. The influence of cyclooxygenase inhibition on the loss of bronchoconstrictor response to repeated bradykinin challenge in asthma. Eur Respir J. 1990;3(8):914-21.
Polosa, R., Lai, C. K., Robinson, C., & Holgate, S. T. (1990). The influence of cyclooxygenase inhibition on the loss of bronchoconstrictor response to repeated bradykinin challenge in asthma. The European Respiratory Journal, 3(8), pp. 914-21.
Polosa R, et al. The Influence of Cyclooxygenase Inhibition On the Loss of Bronchoconstrictor Response to Repeated Bradykinin Challenge in Asthma. Eur Respir J. 1990;3(8):914-21. PubMed PMID: 2127257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The influence of cyclooxygenase inhibition on the loss of bronchoconstrictor response to repeated bradykinin challenge in asthma. AU - Polosa,R, AU - Lai,C K, AU - Robinson,C, AU - Holgate,S T, PY - 1990/9/1/pubmed PY - 1990/9/1/medline PY - 1990/9/1/entrez SP - 914 EP - 21 JF - The European respiratory journal JO - Eur. Respir. J. VL - 3 IS - 8 N2 - Bradykinin is a naturally occurring nonapeptide which may contribute to the pathogenesis of bronchial asthma. When inhaled by asthmatic subjects it is a potent bronchoconstrictor, but with repeated challenge airways responsiveness to the peptide decreases markedly. In vitro studies suggest that loss of bradykinin responsiveness may be due to the secondary generation of relaxant prostanoids. We have used the potent cyclooxygenase inhibitor flurbiprofen to investigate the potential role of prostanoid generation in bradykinin tachyphylaxis in eight asthmatic patients. The effects of oral flurbiprofen (150 mg) and matched placebo were observed on two consecutive dose response studies with inhaled bradykinin and histamine in a double-blind, randomized study. Venous blood was taken to measure the serum concentration of thromboxane B2 (TxB2) as a check on the extent of cyclooxygenase blockade achieved by flurbiprofen. Following recovery from the first challenge with bradykinin, the asthmatic airways showed a reduced response to a second challenge with this nonapeptide, the provocative concentration producing a 20% fall from baseline (PC20) increasing from 0.07 to 0.42 mg.ml-1 (p less than 0.01). The airway response to inhaled histamine after the second bradykinin challenge was not significantly changed. In the presence of demonstrable cyclooxygenase inhibition, flurbiprofen failed to prevent the development of reduced responsiveness to bradykinin observed on the second challenge, the PC20 increasing from 0.10 to 0.48 mg.ml-1 (p less than 0.01). This study demonstrates that repeated exposure to inhaled bradykinin results in loss of the bronchoconstrictor response which appears specific for this agonist and not secondary to the increased generation of protective prostanoids. SN - 0903-1936 UR - https://www.unboundmedicine.com/medline/citation/2127257/The_influence_of_cyclooxygenase_inhibition_on_the_loss_of_bronchoconstrictor_response_to_repeated_bradykinin_challenge_in_asthma_ L2 - http://www.diseaseinfosearch.org/result/633 DB - PRIME DP - Unbound Medicine ER -