Natriuretic Peptides: It Is Time for Guided Therapeutic Strategies Based on Their Molecular Mechanisms

Abstract

Natriuretic peptides (NPs) are the principal expression products of the endocrine function of the heart. They exert several beneficial effects, mostly mediated through guanylate cyclase-A coupled receptors, including natriuresis, diuresis, vasorelaxation, blood volume and blood pressure reduction, and regulation of electrolyte homeostasis. As a result of their biological functions, NPs counterbalance neurohormonal dysregulation in heart failure and other cardiovascular diseases. NPs have been also validated as diagnostic and prognostic biomarkers in cardiovascular diseases such as atrial fibrillation, coronary artery disease, and valvular heart disease, as well as in the presence of left ventricular hypertrophy and severe cardiac remodeling. Serial measurements of their levels may be used to contribute to more accurate risk stratification by identifying patients who are more likely to experience death from cardiovascular causes, heart failure, and cardiac hospitalizations and to guide tailored pharmacological and non-pharmacological strategies with the aim to improve clinical outcomes. On these premises, multiple therapeutic strategies based on the biological properties of NPs have been attempted to develop new targeted cardiovascular therapies. Apart from the introduction of the class of angiotensin receptor/neprilysin inhibitors to the current management of heart failure, novel promising molecules including M-atrial natriuretic peptide (a novel atrial NP-based compound) have been tested for the treatment of human hypertension with promising results. Moreover, different therapeutic strategies based on the molecular mechanisms involved in NP regulation and function are under development for the management of heart failure, hypertension, and other cardiovascular conditions.

Liraglutide ameliorates TAC-induced cardiac hypertrophy and heart failure by upregulating expression level of ANP expression

“…Its diverse physiological impacts on the cardiovascular and renal systems, including natriuresis, diuresis, vasorelaxation, reduction of blood volume, and inhibition of the renin-angiotensin-aldosterone system (RAAS), have been elucidated [ 46 ]. The modulation of ANP levels and activity has recently become a focal point in clinical research, presenting promising therapeutic avenues for heart failure [ 46 , 47 ]. Our findings highlight the significant role of ANP upregulation and its influence on balancing ER stress and autophagy in the cardiac protective effects of liraglutide administration.…”

Novel Strategies in Diagnosing Heart Failure with Preserved Ejection Fraction: A Comprehensive Literature Review

“…However, the role of NPs in HFpEF is controversial, and their levels should be carefully evaluated on a case-by-case basis and corroborated by other imaging parameters [ 32 ]. Limited data are available regarding NPs in patients with HFpEF [ 33 ], and recent studies suggested that elevated circulating levels of NPs are strong predictors of adverse and fatal CV events in these patients [ 34 , 35 ].…”

Kidney Renin Release under Hypoxia and Its Potential Link with Nitric Oxide: A Narrative Review

“…Natriuretic peptides: Natriuretic peptides are hormones secreted from the heart to promote Na + excretion in the kidneys. Currently, there are three known peptides in the natriuretic peptides family: atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) [84]. ANP is hypoxia-responsive and its circulating levels are increased by decreased clearance due to downregulation of the natriuretic peptide receptor-C in hypoxia [85].…”