Bradykinin-induced bronchoconstriction in guinea pig in vivo: role of neural mechanisms.
The mechanism of bradykinin-induced bronchoconstriction was studied in anesthetized guinea pigs after both i.v. administration and direct airway instillation. We monitored airway opening pressure as an index of airway caliber, and the provocative dose of bradykinin required to produce 100% increase in airway opening pressure (PD100) was determined. Animals were pretreated with propranolol (1 mg/kg i.v.) to inhibit adrenergic bronchodilatation. After i.v. administration, the bronchoconstrictor dose-response curve to bradykinin (PD100 = 0.93 nmol/kg) was shifted significantly to the right by atropine (PD100 = 2.34 nmol/kg, P less than .05) and indomethacin (PD100 = 61.7 nmol/kg, P less than .05). Depletion of tachykinins by capsaicin pretreatment had no significant effect on the response to i.v. bradykinin. After tracheal instillation, the bronchoconstrictor dose-response curve to bradykinin (PD100 = 24.5 nmol) was shifted to the right by atropine (PD100 greater than 150 nmol, P less than .05) and capsaicin pretreatment (PD100 greater than 150 nmol, P less than .05). After atropine the response to instilled bradykinin was almost abolished in capsaicin-pretreated animals. Indomethacin had no effect on the bronchoconstrictor response to instilled bradykinin. We conclude that i.v. bradykinin causes bronchoconstriction predominantly by the release of cyclooxygenase products but that a cholinergic reflex is also involved, whereas sensory neuropeptides are not important. By contrast the bronchoconstrictor response to instilled bradykinin is mediated by neural mechanisms involving both cholinergic nerves and sensory neuropeptides but not by cyclooxygenase products.
Ichinose
M
M
Department of Thoracic Medicine, National Heart & Lung Institute, London, United Kingdom.
Belvisi
M G
MG
Barnes
P J
PJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000294:innervation; D001985:Bronchial Provocation Tests; D002211:Capsaicin / Q000494:pharmacology; D003251:Constriction, Pathologic; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D007322:Instillation, Drug; D008297:Male; D011433:Propranolol / Q000494:pharmacology
D001285:Atropine; D011433:Propranolol; D002211:Capsaicin; D001920:Bradykinin; D007213:Indomethacin