What is the rationale for coadministration of an ARB with neprilysin inhibitors?
Neprilysin, also known as neutral endopeptidase, is a zinc-dependent metalloprotease that inactivates several vasoactive peptides, including the natriuretic peptides, adrenomedullin, bradykinin, and substance P, each of which has an important role in the pathogenesis and progression of HF. Because angiotensin II is also a substrate for neprilysin, neprilysin inhibitors raise angiotensin levels, which explains the rationale for coadministration of an ARB.