Modulation of nonadrenergic noncholinergic neural bronchoconstriction by bradykinin in anesthetized guinea pigs in vivo

M Miura, MG Belvisi and PJ Barnes

National Heart and Lung Institute, Department of Thoracic Medicine, London, United Kingdom.

The modulatory effect of bradykinin on excitatory nonadrenergic noncholinergic (e-NANC) neural constrictor responses was examined in anesthetized guinea pig airways in vivo. e-NANC responses were obtained by bilateral vagal stimulation in the presence of atropine (1 mg/kg i.v.) and propranolol (1 mg/kg i.v.). Indomethacin (5 mg/kg i.v.) and captopril (1 mg/kg i.v.) were pretreated to avoid the indirect effects of bradykinin by producing prostaglandins and to prevent endogenous breakdown of bradykinin, respectively. Bradykinin (0.01-1 nmol/kg i.v.) potentiated e-NANC responses in a dose-dependent manner. The potentiation was significant with 0.1 and 1 nmol/kg of bradykinin, 22.7 +/- 3.2% (mean +/- S.E.; P < .01) and 34.5 +/- 4.7% (P < .01), respectively), compared with that in sham-injected control animals (- 4.7 +/- 3.6%). The potentiation of e-NANC responses by bradykinin (1 nmol/kg i.v.) was abolished by the subsequent administration of a bradykinin B2 receptor antagonist, HOE140 (0.1 mumol/kg i.v.), that was without effect on e-NANC responses by itself. The contraction induced by exogenous administration of substance P (1 nmol/kg i.v.) was not affected by the same dose of i.v. bradykinin; the change in substance P- induced bronchoconstriction was 9.2 +/- 8.3% with and 3.2 +/- 3.6% without bradykinin (P > .05). These results suggest that bradykinin potentiates e-NANC responses in guinea pig airways in vivo via B2 receptors which are possibly on prejunctional sites.

Volume 268, Issue 1, pp. 482-486, 01/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics

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