Effect of a bradykinin receptor antagonist, HOE 140, against bradykinin- and vagal stimulation-induced airway responses in the guinea-pig

Abstract

We have investigated the effect of inhaled HOE 140, a novel bradykinin B2 receptor antagonist, against bradykinin- and vagal stimulation-induced airway microvascular leakage and bronchoconstriction in anesthetized guinea-pigs. Lung resistance was measured for 6 min after challenge, followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. Bradykinin was given by inhalation (1 mM, 45 breaths) and bilateral vagus nerves were stimulated electrically during a 5-min period (3 and 10 Hz, 5 V, pulse width of 5 ms), both of which caused a significant increase in lung resistance and leakage of dye in the airway. HOE 140 (20 and 200 microM, 60 breaths) completely abolished both the airway effects induced by bradykinin, whereas even the higher dose of HOE 140 had no effect against those induced by electrical vagal stimulation. In conclusion, airway microvascular leakage and bronchoconstriction induced by inhaled bradykinin are mediated by activation of bradykinin B2 receptors in the guinea-pig. In contrast, mechanisms via bradykinin B2 receptors do not play an important role in the acute airway responses induced by vagal stimulation.