Neutral endopeptidase-24.11 inhibitors: from analgesics to antihypertensives?

A limited number of ectoenzymes appear to be involved in inactivating circulating regulatory peptides. The widely distributed angiotensin-converting enzyme controls the concentration of angiotensin II in the blood, thereby limiting its vasoconstrictor effects. Inhibitors of this enzyme, such as captopril and enalapril, are clinically used as antihypertensives. Neutral endopeptidase-24.11 is known to be involved in inactivating opioid peptides in the CNS and much research has focused on the use of its inhibitors in manipulating endogenous pain-control mechanisms. Recent evidence that this metallopeptidase inactivates atrial natriuretic peptide, summarized here by Bernard Roques and Ann Beaumont, has led to a re-evaluation of the potential use of its inhibitors as novel diuretics and antihypertensive agents.