Pharmacological modulation of the natriuretic peptide system

The natriuretic peptide (NP) system is a cardioprotective hormonal system that fails to meet its cardioprotective end point during the development of cardiovascular complications such as hypertension and heart failure. The use of NPs or orally-active drugs that enhance the function of the NP system, are being explored for the treatment of such disorders. Much of the recent research has focused on vasopeptidase inhibitors that can inhibit neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) and thereby augment NP signalling while attenuating the renin–angiotensin–aldosterone system. These drugs offer several beneficial effects over conventional ACE inhibitors but the vasoactive peptide bradykinin, which is partly responsible for their beneficial effects, leads to serious side effects such as angioedema. The hope that these compounds will replace conventional drugs is fading away but they might be useful in targeted refractory populations immune to conventional drugs. The trends from the recent published patents suggest that pharmaceutical companies are exploring new strategies that include inhibition of endothelin-converting enzyme along with ACE and/or NEP. This comprehensive review will address the patents as well as basic and clinical pharmacology of leading compounds that exploit various strategies to modulate the NP system. This includes recombinant NPs, NP receptor ligands, vasopeptidase inhibitors and novel molecules that offer new strategic insights into the modulation of the NP system for the treatment of cardiovascular complications.