Cross talk on therapeutic strategies: natriuretic peptides and inhibiting neprilysin in hypertension management

Hypertension, a prevalent cardiovascular condition globally, remains a significant public health concern due to its association with increased cardiovascular morbidity and mortality. Despite the availability of various antihypertensive therapies, achieving optimal blood pressure control in patients remains a challenge. Valsartan/sacubitril (ARNi), marketed as Entresto by Novartis, combines valsartan, an angiotensin receptor blocker, with sacubitril, an inhibitor of neprilysin. Neprilysin is responsible for breaking down natriuretic peptides and other vasoactive substances. Inhibiting neprilysin prevents the degradation of natriuretic peptides, enhancing their beneficial effects on blood pressure regulation. Natriuretic Peptides, including atrial natriuretic peptide (ANP) and brain natriuretic peptides (BNP), play pivotal roles in regulating blood pressure and cardiovascular homeostasis by promoting vasodilation, natriuresis, and antagonizing the renin-angiotensin-aldosterone system. Therefore, this combo drug lessens sensitivity to natriuretic peptides and tackles the processes in hypertension that activate the renin-angiotensin-aldosterone system. This review provides an overview of how natriuretic peptides (NPs) contribute to blood pressure regulation for the treatment of hypertension through inhibiting neprilysin. It highlights the ARNi's dual action that works synergistically by blocking the harmful effects of angiotensin II on blood vessels while simultaneously increasing the levels of beneficial natriuretic peptides.Schematic representation of the mechanism of action of ARNi. Abbreviation: -Renin angiotensin aldosterone system (RAAS), Natriuretic peptides (NP), Atrial Natriuretic peptide (ANP), Brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), Angiotensin II (Ang II), Angiotensin receptor neprilysin inhibitor (ARNI). Schematic representation of the mechanism of action of ARNi. Abbreviation: -Renin angiotensin aldosterone system (RAAS), Natriuretic peptides (NP), Atrial Natriuretic peptide (ANP), Brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), Angiotensin II (Ang II), Angiotensin receptor neprilysin inhibitor (ARNI).