[Significance of tachyphylaxis induced by repeated bradykinin inhalation in bronchial asthma].

Bradykinin (Bk) is a potent bronchoconstrictor agent which may contribute to the pathogenesis of bronchial asthma. Recently we have shown that repeated bronchial challenge with this agonist in asthmatics produced a specific loss of responsiveness. In vitro studies suggest that this phenomenon may be due to generation of protective prostaglandins. In this study we investigated whether flurbiprofen (F) pretreatment inhibited Bk tachyphylaxis. The efficacy of F was demonstrated by the total suppression of whole blood TxB2 formation. In addition, a time-course study of the tachyphylactic response was carried out. Refractoriness in response to inhaled Bk occurred in all subjects. The mean PC20 Bk increased from 0.07 to 0.41 mg/ml with consecutive inhalation tests after placebo. Even in the presence of demonstrable cyclooxygenase inhibition, no effect of F was observed in inhibiting Bk tachyphylaxis the mean PC20 Bk still increasing from 0.10 to 0.47 mg/ml. Tachyphylaxis was still present at 6 h, but not in all subjects at 24 h. This study demonstrated that release of protective prostaglandins in the airway after Bk stimulation does not account for the loss of responsiveness following repeated exposure to Bk. At least 24 h should separate Bk inhalations to avoid tachyphylaxis. A possible mechanism of this phenomenon is discussed.