Natriuretic peptides are a family of hormones, containing a 17-amino acid ring, that regulate the water-electrolyte balance in the body. These include atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP).
Natriuretic peptides bind with different affinities to three plasma membrane receptors, NPR-A (GC-A), NPR-B (GC-B), and NPR-C: NPR-A binds both ANP and BNP, NPR-B binds CNP, and NPR-C binds all three, ANP, BNP, and CNP.
ANP is a 28-amino acid hormone that is mainly produced by cardiac myocytes in right atrium. For local regulation, ANP and its truncated versions are also produced in other tissues, including the brain, lungs, and adipose tissue. Plasma half-live of ANP is ∼2-3 min. ANP is degraded by circulating and cell-surface enzymes, and intracellularly after being bound to receptors, including specific natriuretic peptide receptors.
Increase in atrial pressure and myocardial wall stress induces the release of ANP. ANP decreases central venous pressure, inhibits aldosterone secretion, and reduces sympathetic tone. Large dose of ANP increases renal blood flow and dilates afferent arterioles. In physiological doses it inhibits tubular Na+ reabsorption and increases excretion of water.
ANP suppresses signalling of VEGF and attenuates angiogenesis.
BNP in humans is a 32-amino acid hormone that is mainly released from the heart ventricles. Plasma concentrations of BNP are increased with age and in heart and kidney diseases. Plasma half-live of BNP is ∼4 min.
Reduced coronary vasoreactivity is one of the earliest abnormalities in the development of CAD. An inverse association between plasma BNP levels and coronary vasoreactivity has been observed in patients with dilated cardiomyopathy, but not in healthy young subjects, with myocardial perfusion measurement using [15O]H2O PET (Sundell et al., 2011).
Active CNP includes two variants, composed of 22 or 53 amino acids (CNP-22 and CNP-53). Both forms are produced by endothelial cells in variety of tissues, participating probably in local regulation in autocrine or paracrine manner, especially in the bone, brain, and blood vessels. In the plasma, CNP-22 is the dominant form, and its half-life is ∼2-3 min.
High levels of CNP have been seen in atherosclerotic-like plaques in animal models (Liu et al., 2010).
Natriuretic peptide receptor A (NPR-A)
NPR-A is guanylyl cyclase (GC-A), and binding of ANP and ANB leads to increased [cGMP]. NPR-A functions as a homodimer; two NPR-A are needed to bind one substrate molecule. NPR-A is highly expressed in renal arterioles, glomeruli, and medulla, in adrenal zona glomerulosa, in endothelial cells, cerebellum and pituitary, and adipose tissue. Low expression is seen in the heart and ileum.
NPR-A expression is increased in angiogenesis, and could be targeted in imaging of tumours.
Natriuretic peptide receptor B (NPR-B)
NPR-B is guanylyl cyclase (GC-B), and binding of CNP to the homodimer leads to increased [cGMP]. NPR-B is highly expressed in the pituitary and adrenal glands, uterus, and in the central nervous system. In the heart NPR-B is expressed in non-myocyte cells.
Natriuretic peptide receptor C (NPR-C)
NPR-C has a similar extracellular domain as NRP-A and NPR-B, but it lacks the intracellular guanylyl cyclase. Intracellular domain participates in inhibition of adenylyl cyclase, thus reducing [cAMP]. NPR-C is by far the most abundant of natriuretic peptide receptors. NPR-C has similar affinity for ANP, BNP, CNP, and analogous peptides. In the kidneys, NPR-C is the most abundant of natriuretic peptide receptors, with very high expression in glomeruli and large vessels, but no expression in the medulla. NPR-C is also expressed in the heart and adrenal glands.
Since NPR-C can bind all natriuretic peptides and peptide fragments, it has been targeted in PET imaging of angiogenesis, cancer, and atherosclerotic plaques (Liu et al., 2010; Liu et al., 2011; Pressly et al., 2013; Woodard et al., 2016).
Bie P. Natriuretic peptides and normal body fluid regulation. Compr Physiol. 2018; 8: 1211-1249. doi: 10.1002/cphy.c180002.
Naganawa Y, Nishikimi T, Kuwahara K. Atrial and brain natriuretic peptides: hormones secreted from the heart. Peptides 2018 (in press). doi: 10.1016/j.peptides.2018.05.012.
Created at: 2018-08-08
Updated at: 2018-08-09
Written by: Vesa Oikonen