Effect of thromboxane A2-receptor antagonist on bradykinin-induced bronchoconstriction in asthma

J Appl Physiol (1985). 1996 Jun;80(6):1973-7. doi: 10.1152/jappl.1996.80.6.1973.

Abstract

The role of the thromboxane A2 (TxA2) receptor in bradykinin-induced bronchial responses was investigated in this study by using a selective and potent TxA2-receptor antagonist BAY u 3405. Eleven asthmatic subjects were randomized to receive 50 mg of BAY u 3405 or matched placebo in a crossover and double-blind fashion. Ninety minutes after dosing, serum was taken for drug assay, and subjects underwent provocation with bradykinin or prostaglandin D2 (PGD2) to determine bronchial responsiveness [provocative concentration of agonist required to produce a 20% fall in forced expiratory volume in 1 s from the postdiluent baseline (PC20)]. Pretreatment with BAY u 3405 caused a twofold doubling-dilution reduction in bronchial reactivity to PGD2; the geometric mean PC20 values were 0.132 (0.015-0.871) and 0.034 (0.008-0.095) mg/ml, respectively, for active and placebo days (P = 0.001). There was, however, no significant difference in PC20 values for bradykinin between active and placebo treatment days. We have demonstrated that BAY u 3405 caused a significant inhibition of bronchconstriction induced by inhaled PGD2 but had no influence on bronchial responsiveness to inhaled bradykinin. This study suggests therefore that TxA2 receptors do not play a role in bradykinin-induced bronchoconstriction in asthma.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Asthma / drug therapy*
  • Bradykinin / pharmacology*
  • Bronchoconstriction / drug effects*
  • Carbazoles / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Receptors, Thromboxane / antagonists & inhibitors*
  • Sulfonamides / therapeutic use*

Substances

  • Carbazoles
  • Platelet Aggregation Inhibitors
  • Receptors, Thromboxane
  • Sulfonamides
  • ramatroban
  • Bradykinin