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Since the discovery of atrial natriuretic peptide by de Bold and colleagues in 1981, research into the natriuretic peptide (NP) system has expanded enormously over the past 25 years.1 It has moved beyond the role of an endocrine system that modulates volume and pressure homoeostasis in response to increased myocardial wall stress by its effects on the cardiac and renal function, through natriuresis, diuresis, vasodilatation and positive lusitropism. Increasing evidence has now established that the natriuretic peptides possess anti-fibrotic, anti-hypertrophic, anti-inflammatory, cytoprotective properties on the myocardium, in addition to suppression of the renin–angiotensin–aldosterone system, sympathetic outflow, arginine vasopressin and endothelin.2
The NP family is growing and currently consists of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), which are produced predominantly from atria and ventricles, respectively, and also from cardiac fibroblasts; C-type natriuretic peptide (CNP) from the vascular endothelium and central nervous system; dendroaspis natriuretic peptide (DNP) synthesised based on the sequence of the DNP originally isolated from venom of Dendroaspis augusticeps (the green mamba snake) with unknown clinical role at present; and urodilatin, an isoform of ANP secreted into the luminal part of distal nephrons of the kidneys.3 Additional natriuretic-like peptides have also been isolated from the venom of other snake species.2
ANP, BNP and CNP are synthesised as pro-hormones and cleaved by peptidases into C-terminal active hormones and the larger, biologically inactive N-terminal pro-hormone fragments. The biological actions of the NPs are mediated by binding to NP receptors, leading to activation of particulate guanylyl cyclase and production of an intracellular second messenger, cyclic guanosine monophosphate (cGMP), which ultimately interacts with cGMP-dependent protein kinases, cGMP-gated ion channels and phosphodiesterases to produce effects in different tissues and …
Competing interests: None.