Modulation of nonadrenergic noncholinergic neural bronchoconstriction by bradykinin in anesthetized guinea pigs in vivo.
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.
Miura
M
M
National Heart and Lung Institute, Department of Thoracic Medicine, London, United Kingdom.
Belvisi
M G
MG
Barnes
P J
PJ
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D006168:Guinea Pigs; D008297:Male; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D013373:Substance P; D001920:Bradykinin