Bradykinin-induced airway inflammation: Contribution of sensory neuropeptides differs according to airway site

Natsuko Nakajima, Masakazu Ichinose, Tsuneyuki Takahashi, Hideyuki Yamauchi, Atsushi Igarashi, Motohiko Miura, Hiroshi Inoue, Tamotsu Takishima, Kunio Shirato

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

We examined the mechanisms of bradykinin-induced airway microvascular leakage in guinea pig airways by measuring extravasation of Evans blue dye. Animals were pretreated with propranolol (1 mg/kg, intravenous) and atropine (1 mg/kg, intravenous) to block the β-adrenergic and muscarinic responses, respectively. Bradykinin (250 nmol) instillation into airways significantly increased the leakage of dye in the trachea, main bronchi, and intrapulmonary airways to the same degree. The bradykinin B2-receptor antagonist HOE140 (500 nmol/kg, intravenous) did not alter basal leakage but almost completely inhibited bradykinin-mediated leakage. By contrast, the neurokinin NK, antagonist FK888 (10 mg/kg, intravenous) partially inhibited bradykinin- induced leakage in trachea (p < 0.01) and main bronchi (p < 0.01), but had no significant effect on intrapulmonary airways. Indomethacin (5 mg/kg, intravenous) had no effect on the plasma leakage after instilled bradykinin. We concluded that the airway inflammatory response to bradykinin administered directly into the airways is mediated by bradykinin B2 receptors and partially mediated by tachykinin release from sensory nerve terminals, whereas cyclooxygenase products have no important role in the response. In the central airways, the contribution of sensory neuropeptides to the bradykinin response is greater than that caused by direct stimulation of the B2 receptor on the endothelium at the postcapillary venule of the bronchial circulation. In contrast, in the peripheral airways, the contribution of direct B2-receptor stimulation on the airway vasculature is greater than that involving sensory neuropeptides.

Original languageEnglish
Pages (from-to)694-698
Number of pages5
JournalAmerican journal of respiratory and critical care medicine
Volume149
Issue number3 I
DOIs
Publication statusPublished - 1994 Mar

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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