EFFECT OF HOE-140, A NEW BRADYKININ RECEPTOR ANTAGONIST, ON BRADYKININ-ACTIVATING AND PLATELET-ACTIVATING FACTOR-INDUCED BRONCHOCONSTRICTION AND AIRWAY MICROVASCULAR LEAKAGE IN GUINEA-PIG

We have investigated the effect of a new bradykinin receptor antagonist, Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin), on bradykinin- and platelet-activating factor (PAF)-induced bronchoconstriction and airway microvascular leakage in anesthetized guinea pigs. Extravasation of Evans blue dye and lung resistance were measured simultaneously. Both i.v. (15 nmol/kg) and inhaled bradykinin (1 mM, 45 breaths) caused a significant increase in lung resistance and leakage of dye at all airway levels. Hoe 140 (100 nmol/kg i.v.) almost completely inhibited these airway responses induced by bradykinin except for dye extravasation in trachea induced by inhaled bradykinin. Inhaled PAF (3 mM, 30 breaths) significantly increased lung resistance and leakage of due at all airway levels, but Hoc 140 had no effect on these responses. Bradykinin-induced bronchoconstriction and airway microvascular leakage are predominantly mediated by activation of B2 receptor, since Hoc 140 is a B2 receptor antagonist. Bradykinin receptor-mediated mechanisms do not play an important role on inhaled PAF-induced bronchoconstriction and microvascular leakage.