Combined inhibition of ACE and neutral endopeptidase represents a logical therapeutic approach for hypertension and heart failure by simultaneously blocking the renin-angiotensin system and enhancing the natriuretic peptide system.
Hypothesis-generating for dual ACE-neprilysin inhibition in hypertension and heart failure; randomized trials needed before clinical adoption.
Combined inhibition of ACE and neutral endopeptidase. The human cardiovascular system is regulated by different haemodynamic, structural and neurohumoral mechanisms. The endothelium and the neurohumoral system play a key role in modulating both vascular tone and structure by producing vasoactive substances involved also as cell-growth. Although the neurohumoral systems are essential in the vascular homeostasis, they can also become maladaptive in conditions such as congestive heart failure. The clinical success of blocking the renin-angiotensin system by angiotensin-converting enzyme (ACE)-inhibitors has led to efforts to block other humoral systems. The neutral endopeptidase, as ACE, is an endothelial cell surface zinc metallopeptidase with similar structure and catalytic site to ACE. Neutral endopeptidase is the major enzymatic pathway for degradation of natriuretic peptides. The natriuretic peptide system can be viewed as the endogenous inhibitor of the renin-angiotensin system. Thus, the combined inhibition of angiotensin-converting enzyme and neutral endopeptidase seems to be the logical way to treat patients with hypertension or heart failure.
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Corti et al. (1999) studied this question.
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