The term vasopeptidase means any
peptidase able to generate or to inactivate a vasoactive
peptide. This term got a more definitive meaning when a new class of drugs, the
vasopeptidase inhibitors, was introduced. These drugs are especially represented by the inhibitors of
angiotensin-converting enzyme (ACE) and
neutral endopeptidase (NEP). ACE is now primarily considered a kininase rather than an
angiotensinase and
ACE-inhibitors have been used successfully in the treatment of many
cardiovascular diseases, including
hypertension and
heart failure. Preliminary results suggest that the use of NEP inhibitors could also contribute to improve prognosis of
cardiovascular diseases.
Vasopeptidase inhibitors simultaneously inhibiting both NEP and ACE have shown to be more effective than currently available
ACE inhibitors. (
Omapatrilat is at present the most clinically advanced in these drugs). However, many side-effects of
vasopeptidase inhibitors have been reported, but the most dangerous is
angioedema which is potentially life threatening. Since this complication is mediated by
bradykinin, and both inhibition of ACE and NEP can produce
bradykinin increasing, it has been suggested that the incidence of
angioedema due to
vasopeptidase inhibitors could be higher compared with that related to
ACE-inhibitors. The FDA raised concern about this adverse effect, and the manufacturer decided to withdraw the application temporarily. In order to identify patients at risk of
angioedema we have recently shown that low plasma levels of
aminopeptidase P, another
enzyme which cabolises
bradykinin, could indicate a predisposition for development of
angioedema in some patients treated with vasoinhibitor drugs.