Guanylyl cyclase / atrial natriuretic peptide receptor-A: role in the pathophysiology of cardiovascular regulation

Abstract

Atrial natriuretic factor (ANF), also known as atrial natriuretic peptide (ANP), is an endogenous and potent hypotensive hormone that elicits natriuretic, diuretic, vasorelaxant, and anti-proliferative effects, which are important in the control of blood pressure and cardiovascular events. One principal locus involved in the regulatory action of ANP and brain natriuretic peptide (BNP) is guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA). Studies on ANP, BNP, and their receptor, GC-A/NPRA, have greatly increased our knowledge of the control of hypertension and cardiovascular disorders. Cellular, biochemical, and molecular studies have helped to delineate the receptor function and signaling mechanisms of NPRA. Gene-targeted and transgenic mouse models have advanced our understanding of the importance of ANP, BNP, and GC-A/NPRA in disease states at the molecular level. Importantly, ANP and BNP are used as critical markers of cardiac events; however, their therapeutic potentials for the diagnosis and treatment of hypertension, heart failure, and stroke have just begun to be realized. We are now just at the initial stage of molecular therapeutics and pharmacogenomic advancement of the natriuretic peptides. More investigations should be undertaken and ongoing ones be extended in this important field.

Pathological Ventricular Remodeling

“…For example, natriuretic peptides such as ANF (atrial natriuretic factor) and BNP (B-type natriuretic peptide) are secreted from cardiomyocytes in response to stress 143 . These peptides, circulating levels of which are elevated in heart failure, have lipolytic effects on adipose tissue, which is specific to primates 144 .…”

The multifaceted role of natriuretic peptides in metabolic syndrome

“…In addition, NPR-A is also known to be involved in stem cell recruitment, angiogenesis, and inflammation along with the regulation of self-renewal and pluripotency of embryonic stem cells [120]. Studies have shown that appropriate BNP expression and its abundance are essential for the maintenance of embryonic stem cells propagation establishing the role of BNP as a novel endogenous regulator of embryonic stem cell proliferation and it may also activate NPR-A which helps in self renewal and pluripotency of embryonic stem cells [121, 122]. Also, ANP is known for its antitumor activity by inhibiting DNA synthesis [123].…”

Lasso Peptides

“…Natriuretic peptides (NPs) are hormones involved in the maintenance of osmotic and cardiovascular homeostasis (Brenner et al 1990;Drewett and Garbers 1994;McGrath et al 2005;Potter et al 2006;Pandey 2011). They are distributed in vertebrates including mammals, amphibians, reptiles and fishes (Takei 2000) and homologous peptides are found in plants (Vesely and Giordano 1991;Gehring and Irving 2013).…”

“…It elicits natriuretic, diuretic and vasorelaxant effects, thereby reducing blood volume and pressure (Potter et al 2006;Misono et al 2011;Pandey 2011). It also displays anti-fibrosis, anti-proliferative and anti-hypertrophic effects and is involved in the remodelling of the heart and vascular system.…”