ABSTRACT
Omapatrilat (1) (Fig. 1A) is an antihypertensive drug that acts by inhibiting angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) (11). Effective inhibitors of ACE have been used not only in the treatment of hypertension but also in the clinical management of congestive heart failure. NEP, like ACE, is a zinc metalloprotease and is highly efficient in degrading atrial natriuretic peptide (ANP), a 28-amino acid peptide secreted by the heart in response to atrial distension. By interaction with its receptor, ANP promotes the generation of cGMP via guanylate cyclase activation, thus resulting in vasodilatation, natriuresis, diuresis, and inhibition of aldosterone. Therefore, simultaneous potentiation of ANP via NEP inhibition and attenuation of angiotensin II (AII) via ACE inhibition should lead to complementary effects in the management of hypertension and congestive heart failure (12).
