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Dual ACE/NEP inhibitors – more than playing the ACE card

Journal of Human Hypertension volume 20, pages 478–481 (2006)Cite this article

Vasopeptidase inhibition is a novel therapeutic approach in the treatment of cardiovascular diseases such as hypertension and heart failure. The concept of dual inhibition of the two enzymes, angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) by a single molecule has shown major benefits and potentially superiority versus other agents in various experimental models of hypertension, heart failure and renal disease.1 The underlying presumed rationale for the combined inhibition of ACE and NEP is to block the vasoconstrictor angiotensin II (AII) and simultaneously increase the vasodilator, atrial natriuretic peptide (ANP) by decreasing its enzymatic degradation. Furthermore, both vasoactive hormones, AII and ANP appear to have actions beyond their haemodynamic effects. AII meditates proliferation, fibrosis, inflammation and oxidative stress whereas ANP has antiproliferative and antifibrotic effects. Both peptides have been postulated to act as endogenous antagonists to each other.2

On the basis of the positive results with ACE inhibition in a range of cardiovascular diseases, including hypertension, diabetes and renal disease several investigators have started to study the potentially added beneficial effects by blocking other endogenous enzymes involved in peptide activation or degradation. One of these enzymes is NEP, a metallopeptidase similar in structure and distribution to ACE.

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  1. Baker Heart Research Institute, Danielle Alberti JDRF Centre for Diabetes Complications, Wynn Domain, Melbourne, Victoria, Australia

    K A M Jandeleit-Dahm

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  1. K A M Jandeleit-Dahm
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Correspondence to K A M Jandeleit-Dahm.

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Jandeleit-Dahm, K. Dual ACE/NEP inhibitors – more than playing the ACE card. J Hum Hypertens 20, 478–481 (2006). https://doi.org/10.1038/sj.jhh.1002018

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