Functional characterization of the mechanisms underlying bradykinin-induced relaxation in the isolated rat carotid artery

This work aimed to functionally characterize the mechanisms underlying the relaxation induced by bradykinin (BK) in the rat carotid artery. Vascular reactivity experiments, using standard muscle bath procedures, showed that BK (0.1 nmol/L–3 μmol/L) induced relaxation of phenylephrine-pre-contracted rings in a concentration-dependent manner. Endothelial removal strongly attenuated BK-induced relaxation. HOE-140, the selective antagonist of bradykinin B2 receptors concentration-dependently reduced the relaxation induced by BK. Pre-incubation of endothelium-intact rings with l-NAME (100 µmol/L), a non-selective nitric oxide synthase (NOS) inhibitor, l-NAME (100 µmol/L), a selective inhibitor of the eNOS or 7-nitroindazole (100 µmol/L), the selective inhibitor of nNOS, reduced BK-induced relaxation. Conversely, 1400 W (10 nmol/L), a selective inhibitor of iNOS, did not alter the relaxation induced by BK. Surprisingly, indomethacin (10 µmol/L) a non-selective inhibitor of cyclooxygenase (COX) increased BK-induced relaxation in endothelium-intact but not denuded rings. Neither SQ29548 (3 µmol/L), a competitive antagonist of PGH2/TXA2 receptors nor AH6809 (10 µmol/L), an antagonist of PGF2α receptors significantly altered the relaxation induced by BK in endothelium-intact rings. The combination of SQ29548 and AH6809 increased BK-induced relaxation. The present study shows that the vasorelaxant action displayed by BK in the rat carotid is mediated by endothelial B2 receptors and the activation of the NO pathway. The major finding of this work is that it demonstrated functionally that endothelial-derived vasoconstrictor prostanoids (probably PGH2, TXA2 and PGF2α) counteract the vasorelaxant action displayed by BK.