Renin–Angiotensin Blockade Combined With Natriuretic Peptide System Augmentation

C ardiovascular diseases in general and heart failure (HF) in particular are major contributors to death and morbidity in the Western world, where they are also recognized as important drivers of healthcare expenditure. 5] Moreover, ACEi may prevent proteolysis of bradykinin, thus enhancing bradykinin-mediated vasodilatory effects that may counteract the profound vasoconstriction seen in patients with HF. However, despite encouraging results from many clinical trials, ACEiand ARBs-based pharmacotherapy is still far from optimal. ACEi may lose their efficacy over time because of redundant Ang-II-generating pathways and the so-called aldosterone escape, 8 whereas conventional ARBs do not possess the bradykinin-enhancing properties of ACEi and are considered less effective in HF compared with ACEi. he natriuretic peptides (NPs), consisting of atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), and urodilatin, are predominantly generated by the heart, vasculature, kidney, and central nervous system in response to wall stress and number of other stimuli. Importantly the NPs, particularly ANP and BNP, represent the body's own blood pressure (BP)lowering system. Besides promoting vasodilation, NPs counteract pathological growth, fibrosis, and dysfunction of heart, kidneys, brain, and the vasculature. Current NP-augmenting strategies include the design of a number of synthetic NPs and inhibition of neprilysin, the key enzyme responsible for NP breakdown. Dual-acting angiotensin-receptor neprilysin inhibitors (ARNi) are under scientific scrutiny for the treatment of hypertension and HF.