Role played by NK2 receptor and cyclooxygenase activation in bradykinin B2 receptor mediated-airway effects in guinea pigs.
We have investigated the effects of SR-48968, an NK2 receptor antagonist, and indomethacin, a cyclooxygenase inhibitor, against bronchoconstriction and airway microvascular leakage induced by bradykinin (BK) in anesthetized guinea pigs. In addition, we have determined whether these effects were mediated via bradykinin B2 receptor activation, using a B2 receptor antagonist HOE 140. Lung resistance (RL) and extravasation of Evans blue dye into airway tissues were used as indexes of airway caliber and microvascular leakage, respectively. BK (15 nmol/kg i.v.) induced a significant increase in RL and leakage of dye at all airway levels, responses which were completely abolished by HOE 140 (0.13 mg/kg i.v.). SR-48968 (1.5 mg/kg i.v.) had no effect against BK-induced airway effects. Indomethacin (5 mg/kg i.v.) completely blocked the increase in RL and significantly inhibited the leakage of dye in peripheral intrapulmonary airway. In conclusion, bronchoconstriction induced by i.v. BK is mediated by release of cyclooxygenase products but not by stimulation of NK2 receptors, while the airway microvascular leakage only partly involves cyclooxygenase activation. Cyclooxygenase activation may occur following bradykinin B2 receptor stimulation.
Sakamoto
T
T
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Tsukagoshi
H
H
Barnes
P J
PJ
Chung
K F
KF
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D018002:Receptors, Bradykinin; D018041:Receptors, Neurokinin-2; C065679:icatibant; D011451:Prostaglandin-Endoperoxide Synthases; D001920:Bradykinin; D007213:Indomethacin