Experiments were designed to study the effects of converting-enzyme inhibitors (captopril and S 10211) on the endothelium-dependent relaxation to bradykinin in isolated porcine arteries. Rings of femoral arteries with and without endothelium were suspended in organ chambers to record isometric tension. Rings of coronary arteries without endothelium were used as bioassay tissue to record release of endothelium-derived relaxing factor (EDRF) from perfused femoral arteries. In organ chambers, bradykinin induced endothelium-dependent relaxation and, inconsistently, endothelium-independent contraction of the femoral artery rings. The relaxation is mediated by endothelial B2 bradykinin receptors, the contraction through B1 bradykinin receptors. Converting-enzyme inhibitors induced a weak potentiation of the contractile response and weak or no potentiation of the endothelium-dependent relaxation. In the presence of indomethacin, the response to bradykinin was not modified and no potentiation from the inhibitor could be observed. Blockade of the contractile response with a B1 bradykinin antagonist did not unmask a potentiation of the bradykinin endothelium-dependent relaxation by the converting-enzyme inhibitors. However, in the presence of B2 bradykinin antagonist, when high concentrations of bradykinin are required to induce relaxation, converting-enzyme inhibitors potentiated the effects of bradykinin. In contrast, in bioassay conditions with a perfused vascular segment, converting-enzyme inhibitors selectively enhanced the release of EDRF by bradykinin. This effect is observed in the bioassay tissue and in the donor segment. These results suggest that converting enzyme is indeed a powerful modulator of bradykinin action and that other enzymatic pathways of bradykinin metabolism present in the vascular wall could mask its action.
Vasodepressor role of endogenous bradykinin assessed by a bradykinin antagonist.