Biphasic response to bradykinin in isolated porcine iliac arteries is mediated by bradykinin B1 and B2 receptors

Bradykinin-induced responses were studied ill isolated porcine iliac arteries. Relaxation was endothelium dependent and seen at low concentrations (10-(10)10(-8) M) of bradykinin. It was inhibited by the bradykinin B-2-receptor antagonist icatibant (HOE-140) and by the nitric oxide synthase inhibitor N-omega-nitro-L-arginine. Bradykinin-induced relaxation was significantly potentiated by the kininase I carboxypeptidase inhibitor mergepta (10(-6) M). Bradykinin (> 10(-7) M) elicited contraction of preparations with or without endothelium. The contraction was abolished by indomethacin but was not affected by the thromboxane A(2)/prostaglandin H-2-receptor antagonist SQ 29,548. Icatibant and the bradykinin B-1-receptor antagonist desArg(9)[Leu(8)]bradykinin significantly decreased bradykinin-induced contraction regardless of endothelial function. The contraction also was decreased by treatment with mergepta. The bradykinin B-1-receptor agonist desArg(9)-bradykinin contracted endothelium-denuded arterial strips. This contraction was significantly decreased by desArg(9) [Leu(8)] bradykinin but not by icatibant. The desArg(9)-bradykinin-induced contraction also was inhibited by the protein-synthesis inhibitor cycloheximide. Neither bradykinin-induced relaxation nor contraction was affected by the ACE inhibitors enalaprilat or cilazaprilat. In conclusion, bradykinin-induced relaxation of isolated porcine iliac arteries was mediated by endothelial bradykinin B-2 receptors and mainly nih-ic oxide. Bradykinin-induced contraction was endothelium independent, indomethacin sensitive, and probably mediated by bradykinin B-1 (inducible) and B-2, receptors located in the vascular smooth-muscle layer. Kininase I carboxypeptidase, and not ACE, is the main enzyme responsible for bradykinin degradation in these vessels.