Natriuretic peptides and neprilysin inhibition in hypertension and hypertensive organ damage

The family of natriuretic peptides (NPs) discovered in mammalian tissues including cardiac atrium and brain consists of three members, namely, atrial, B- and C-type natriuretic peptides (ANP, BNP, CNP). Since the discovery, basic and clinical studies have been vigorously performed to explore the biological functions and pathophysiological roles of NPs in a wide range of diseases including hypertension and heart failure. These studies revealed that ANP and BNP are hormones secreted from the heart into the blood stream in response to pre- or after-load, counteracting blood pressure (BP) elevation and fluid retention through specific receptors. Meanwhile, CNP was found to be produced by the vascular endothelium, acting as a local mediator potentially serving protective functions for the blood vessels. Because NPs not only exert blood pressure lowering actions but also alleviate hypertensive organ damage, attempts have been made to develop therapeutic agents for hypertension by utilizing this family of NPs. One strategy is to inhibit neprilysin, an enzyme degrading NPs, thereby enhancing the actions of endogenous peptides. Recently, a dual inhibitor of angiotensin receptor-neprilysin was approved for heart failure, and neprilysin inhibition has also been shown to be beneficial in treating patients with hypertension. This review summarizes the roles of NPs in regulating BP, with special references to hypertension and hypertensive organ damage, and discusses the therapeutic implications of neprilysin inhibition.