Bradykinin-induced bronchoconstriction in guinea pig in vivo: Role of neural mechanisms

M. Ichinose, M. G. Belvisi, P. J. Barnes

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105 Citations (Scopus)

Abstract

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 < .05) and indomethacin (PD100 = 61.7 nmol/kg, P < 0.5). 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 > 150 nmol, P < .05) and capsaicin pretreatment (PD100 > 150 nmol, P < .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.

Original languageEnglish
Pages (from-to)594-599
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume253
Issue number2
Publication statusPublished - 1990 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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