Am. J. Respir. Crit. Care Med., Vol 149, No. 3, Mar 1994, 694-698.
Bradykinin-induced airway inflammation. Contribution of sensory neuropeptides differs according to airway site
N Nakajima, M Ichinose, T Takahashi, H Yamauchi, A Igarashi, M Miura, H Inoue, T Takishima and K Shirato
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
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 beta-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 NK1 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.
