Natriuretic Peptides

Abstract

In the 25 years since de Bold et al demonstrated the existence of an atrial natriuretic factor, investigation of the cardiac natriuretic peptides has produced a maturing knowledge base 1,2 identifying the cardiac peptides and addressing stimuli for secretion of atrial (ANP) and B-type (BNP) natriuretic peptides, the processing and release of the mature bioactive carboxy terminal peptides, together with their propeptides and amino terminal fragments, the nature of natriuretic peptide receptors, and the bioactivities of natriuretic peptides (including natriuresis, vasodilatation, suppression of renin-angiotensin-aldosterone and sympathetic nervous activity, and trophic effects inhibiting vascular and cardiac hypertrophy and fibrosis). Less is known of the more recently discovered C-type natriuretic peptide (CNP and its cosecreted amino-terminal peptide, NTproCNP). 3,4 Increasingly, measurements of the B-type peptides have found diagnostic and prognostic application in cardiovascular disease. [5][6][7] The genes for ANP and BNP are in tandem on human chromosome 1. 8 Upstream regulatory regions identified for the BNP gene include an AP1 binding site, serum response elements, M-CAT and GATA sites. 9,10 Translation results in pre-pro BNP from which a 26 amino acid signal peptide is cleaved to produce the 108 amino acid precursor proBNP. This in turn is processed between amino acid residues 76 and 77 resulting in a 32 amino acid biologically active peptide (BNP) from its carboxy terminal plus the remaining amino terminal peptide sequence (NTproBNP 1 to 76). ANP is synthesized as a 126 amino acid precursor and is stored in granules within atrial tissue. 11 During or shortly after secretion, the precursor is processed to an active 28 amino acid carboxy terminal peptide (ANP) and amino terminal ANP (proANP 1 to 98). The amino terminal propeptides NTproANP, NTproBNP, and NTproCNP have no known biological actions. The mature bioactive human forms of ANP, BNP, and CNP all contain a 17 member amino acid ring bound by cysteine-to-cysteine disulphide bonds with 11 of the 16 residues being conserved across ANP, BNP, and CNP. The 3 peptides have varying length amino terminal and carboxy terminal amino acid residue "tails" with CNP essentially lacking any carboxy terminal extension beyond the ring structure. The actions of ANP and BNP are mediated predominantly via the GC-A receptor and those of CNP via the GC-B receptor. All 3 peptides are subject to varying degrees of degradation by neutral endopeptidase (EC 3.4.24.11) and via uptake by the C ("clearance") receptor.ANP and BNP and their receptors are widely distributed in brain, spinal cord, pituitary, kidney, adrenal gland, and vasculature in addition to the heart. Concentrations of immunoreactive ANP and BNP within the heart are up to 3 orders of magnitude higher than elsewhere, and within cardiac atria the concentrations of both peptides are 1 to 2 orders of magnitude higher than in ventricle. 12 CNP is also widely distributed mainly in the vasculature with far lower cardiac ...

Phosphodiesterase inhibitors for the treatment of pulmonary hypertension

“…The natriuretic peptides interact with specific cell membrane receptors [2]. Two subtypes of natriuretic peptide receptor (NPR), NPR-A and NPR-B, are transmembrane guanylyl cyclases (particulate guanylyl cyclases), where the extracellular domain binds atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) or C-type natriuretic peptide and the intracellular domain hydrolyses guanosine triphosphate (GTP) to cGMP.…”

Biomarkers of Left Atrial Volume

“…27 In the presence of volume overload, LVH, and/or LV dysfunction (ie, in pathophysiological situations that commonly occur in ESRD), the synthesis of BNP in the left atrium increases substantially and matches that of ANP. 28,29 Because of the lack of renal clearance, these peptides accumulate in ESRD.…”

Association of N-Terminal Pro B-Type Natriuretic Peptide With Blood Pressure and Pulse Pressure in Elderly People ― A Cross-Sectional Population Study ―

“…Although high SBP could increase cardiac afterload, Macheret et al showed a lack of increase in BNP in middle-aged patients with prehypertension and early stage hypertension. 7 BNP has compensating effects to reduce afterload, including vasodilation, increased sodium excretion, and inhibition of the sympathetic nervous and renin-angiotensin-aldosterone systems, 16 all of which could reduce BP levels. Belluardo et al suggested that the reduction in NT-proBNP concentrations in prehypertension Model 1 was adjusted for age, sex, BMI, serum creatinine, and serum hemoglobin.…”