Cardiovascular Pleiotropic Effects of Natriuretic Peptides

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.

Natriuretic Peptides in the Cardiovascular System: Multifaceted Roles in Physiology, Pathology and Therapeutics

“…Their anti-proliferative, anti-fibrotic, and anti-hypertrophic effects, including the underlying signaling pathways, were largely documented at both cardiac and vascular levels [3]. In this issue, a review of the literature presented by Forte M. et al summarizes the current knowledge on the cardiovascular pleiotropic effects of NPs and highlights the most relevant findings that underscore the NPs system as a key player in the cardiovascular remodeling process [7]. A major strength of this aspect of NPs function was initially provided by genetically modified animal models showing that lack of either the ANP ( Nppa ) or NPRA gene ( Npr-1 ) led to hypertension and marked cardiac hypertrophy, the latter being independent from high blood pressure levels [7].…”

Natriuretic peptides and their usefulness in clinical practise

“…Collected data is suggesting the role of NPR-B in cardiac hypertrophy regulation. It was also proven that CNP reduces proliferation of smooth muscle cells in vessels induced by platelet-derived growth factor and also reduces tunica interna damage in common carotid arteries among rats that suffered vessel damage [5].…”

“…Apart from systemic functions, BNP also shows local effects on muscle tissue in the heart. It was proven that BNP infusion suppresses TGF-β infused fibroblast proliferation and reduces expression of fibrosis-related genes, myofibroblasts conversion and inflammation [5].…”

Key Player in Cardiac Hypertrophy, Emphasizing the Role of Toll-Like Receptor 4

“…They include atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which are induced by pathological stimulation and are synthesized mainly in cardiac tissues, causing a series of biological effects such as diuresis, natriuresis, vasorelaxation, thus serving as protective molecules of the heart (128). Meanwhile, these peptides have been shown to stimulate production of cyclic guanosine monophosphate and protein kinases G by interacting with the natriuretic peptide receptor, showing the anti-hypertrophic effects in the cardiac hypertrophy model (128,129). Due to NPs' beneficial effects, Nesiritide, a synthetic BNP, has been applied to patients with acute decompensated heart failure and has achieved sound therapeutic efficacy (130).…”