Figure 5.

Illustration of two different mechanisms by which neprilysin inhibitors may potentiate bradykinin receptor-mediated actions. Firstly, neprilysin inhibitors may increase bradykinin receptor occupancy by inhibiting bradykinin degradation and increasing bradykinin levels in the vicinity of the receptor. Secondly, neprilysin inhibitors may promote cross-talk between the neprilysin-inhibitor complex and the bradykinin receptor. Bradykinin receptor antagonists, anti-bradykinin antibodies, and kallikrein inhibitors have different effects on these two mechanisms of neprilysin inhibitor-induced potentiation of bradykinin receptor-mediated actions. A bradykinin receptor antagonist that occupies the bradykinin receptor can prevent both mechanisms of neprilysin inhibitor-induced potentiation of bradykinin receptor-mediated actions. However, bradykinin antibodies that prevent bradykinin binding to its receptor by sequestering bradykinin, and kallikrein inhibitors that prevent bradykinin binding to its receptor by preventing its formation, do not impact on cross-talk between the neprilysin-inhibitor complex and the bradykinin receptor.