Given the complexity of RAS interconnections with other systems such as bradykinins, natriuretic peptides and prostaglandins, its manipulation has often produced differing results—as with omapatrilat (a neprilysin blocker combined with an ACE inhibitor), where the beneficial effects of blocking neprilysin are counterbalanced by the risk of angioedema due to the double blockade in the breakdown of bradykinin (34). Here, MME is linked to angioedema.