We have investigated the effects of bradykinin (Bk) antagonists on Bk-induced airway microvascular leakage and bronchoconstriction in mechanically ventilated guinea pigs by simultaneous measuring extravasation of Evans blue dye and airway opening pressure (Pao). Bradykinin (1 μg/kg intravenously) significantly increased leakage of dye in trachea, main bronchi, and intrapulmonary airways, and increased Pao, indicating airway narrowing. The selective Bk B2 antagonist D-Arg-[Hyp3-Thi5.8-D-Phe7]-Bk (NPC 349; 400 μg/kg intravenously) did not alter basal leakage, but when given 2 min before Bk, significantly inhibited the Bk-induced plasma extravasation by 99.8% in the trachea (p < 0.05), by 75.9% in main bronchi (p < 0.05), by 83.5% in proximal intrapulmonary airways (p < 0.05), and by 91.5% in distal intrapulmonary airways (p < 0.05). NPC 349 also reduced the increase in Pao induced by Bk by 73.5% (p < 0.05) without affecting the basal Pao. However, NPC 349 had no inhibitory effect on Bk-induced leak or bronchoconstriction when given 30 min before Bk. By contrast, the B1 antagonist des Arg9-Leu8-Bk (500 μg/kg intravenously) had no effect on the Bk-increased plasma extravasation and Pao. We conclude that Bk increases airway plasma leakage and bronchoconstriction via activation of B2 receptors.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine