Cardiovascular Pleiotropic Effects of Natriuretic Peptides.

Forte Forte,Madonna Madonna,Versaci Versaci,Frati Frati,Valenti Valenti,Sciarretta Sciarretta,Zoccai Zoccai,Schiavon Schiavon

doi:10.3390/ijms20163874

Abstract

Atrial natriuretic peptide (ANP) is a cardiac hormone belonging to the family of natriuretic peptides (NPs). ANP exerts diuretic, natriuretic, and vasodilatory effects that contribute to maintain water–salt balance and regulate blood pressure. Besides these systemic properties, ANP displays important pleiotropic effects in the heart and in the vascular system that are independent of blood pressure regulation. These functions occur through autocrine and paracrine mechanisms. Previous works examining the cardiac phenotype of loss-of-function mouse models of ANP signaling showed that both mice with gene deletion of ANP or its receptor natriuretic peptide receptor A (NPR-A) developed cardiac hypertrophy and dysfunction in response to pressure overload and chronic ischemic remodeling. Conversely, ANP administration has been shown to improve cardiac function in response to remodeling and reduces ischemia-reperfusion (I/R) injury. ANP also acts as a pro-angiogenetic, anti-inflammatory, and anti-atherosclerotic factor in the vascular system. Pleiotropic effects regarding brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were also reported. In this review, we discuss the current evidence underlying the pleiotropic effects of NPs, underlying their importance in cardiovascular homeostasis.

Highlights

Atrial natriuretic peptide (ANP) was the first member of the natriuretic peptides (NPs) family to be discovered, in 1981 [1,2,3]
We summarized the relevant literature about the role of NPs, and in particular of ANP, in the improvement of cardiac and vascular remodeling in different stress conditions
In vivo and in vitro studies revealed that local ANP secretion by cardiac and endothelial cells play important pleiotropic functions through autocrine and paracrine effects

Summary

Introduction

Atrial natriuretic peptide (ANP) was the first member of the natriuretic peptides (NPs) family to be discovered, in 1981 [1,2,3]. NPs are synthetized as pre-hormones and subsequently cleaved into the biological active carboxy terminal forms (α-ANP, BNP-32, CNP-22), together with their respective amino-terminal ends. For these reasons, it is recommended to consider the level of BNP and proBNPs together in HF patients [22]. It is strongly recommended that NPs levels should be evaluated in conjunction with other clinical parameters, such as renal function, body mass index, and cardiac imaging [23] Besides their systemic effects, accumulating lines of evidence indicate that ANP has beneficial pleiotropic effects on the cardiovascular system at baseline and in response to stress. We discuss the available human evidence regarding the pleiotropic effects of ANP in the cardiovascular system

Overview of ANP Metabolism

ANP and Cardiac Pleiotropic Effects

ANP and Vascular Pleiotropic Effects

Therapeutic Interventions Targeting NPs

Conclusions and Perspectives