Bradykinin-induced airway microvascular leakage and bronchoconstriction are mediated via a bradykinin B2 receptor.
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 microgram/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 micrograms/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 less than 0.05), by 75.9% in main bronchi (p less than 0.05), by 83.5% in proximal intrapulmonary airways (p less than 0.05), and by 91.5% in distal intrapulmonary airways (p less than 0.05). NPC 349 also reduced the increase in Pao induced by Bk by 73.5% (p less than 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 micrograms/kg intraveneously) 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.
Ichinose
M
M
Department of Thoracic Medicine National Heart and Lung Institute, Brompton Hospital, London, United Kingdom.
Barnes
P J
PJ
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000502:physiology*; D002199:Capillary Permeability / Q000502:physiology*; D006168:Guinea Pigs; D008297:Male; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D012137:Respiratory System / Q000098:blood supply*
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C053748:B 4162; C051090:bradykinin, Leu(8)-des-Arg(9)-; D001920:Bradykinin