Rethinking the Renin-Angiotensin System and Its Role in Cardiovascular Regulation

Angiotensin-converting enzyme (ACE) plays a pivotal role in the renin-angiotensin system (RAS) and ACE-inhibitors are widely used in several clinical conditions, including hypertension and heart failure. Recently, a homologue of ACE, ACE2 has been discovered. Both ACE and ACE2 are emerging as key enzymes of the RAS, where ACE2 may play a role as negative regulator of ACE. Moreover, ACE2 appears to be an important enzyme outside the classical RAS, as it hydrolyzes apelins, dynorphin A 1-13, des-Arg-bradykinin and other peptide substrates. The precise interplay between tissue ACE, ACE2, and their substrates and by-products are presently still unclear.