Natriuretic peptides, ANP, BNP, CNP
Natriuretic peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are a family of endogenous polypeptide mediators mainly of cardiac origin with natriuretic and vasodilator effects. They are sometimes named cardiac hormones.
The discovery of ANP results from histological observation of “dense bodies” in atrium explaining its denomination atrial) whose volume increased in animals receiving a sodium overload. The injection of extracts of these “dense bodies” induced diuresis and natriuresis.
ANP is a 28-amino acid polypeptide secreted by atrial myocytes in response to distension.
BNP, thus named because it was first discovered in brain, is a 32-amino acid mainly secreted by ventricles in response to stretch.
CNP is a 22-amino acid polypeptide formed in brain and in vascular endothelium.
The chemical structure of ANP, BNP and CNP presents a ring formed by a disulfide bond between 2 cysteine residues.
Metabolism
ANP, BNP and CNP are polypeptides resulting from successive cleavages of larger peptides, called preprohormones and prohormones.
ANP and BNP, formed in heart are secreted in plasma where their respective half-life is about 1 min and 20 min, respectively. CNP is little secreted and its circulating level is very low.
In plasma, they are inactived by two mechanisms, enzymatic hydrolysis and receptor-mediated endocytosis. Neutral endopeptidase, an endothelial cell-surface zinc metallo-enzyme-, hydrolyzes these peptides. A natriuretic receptor, NPR-C present in vascular wall , binds these peptides which are internalized by endocytosis and degraded. NPR-C has also a signalling function leading to vasodilation by activatuion of potassium channels.
ANP and BNP secretion is increased by sodium overload, increase of extracellular volume, distension of auricles and ventricles.
Effects
ANP and BNP activate specific receptors, in particular guanylate cyclase, which induces an increase of intracellular cyclic GMP. This activation has many consequences:
- Renal:
- Increase of glomerular filtration and aqueous diuresis
- Enhanced urinary excretion of sodium (= natriuresis) and of other electrolytes, phosphate, magnesium, calcium, potassium
- Cardiov ascular:
- Vasodilation and decrease of arterial pressure
- Decrease of vascular reactivity to vasoconstrictive agents
- Dilatation of the renal afferent arterioles which increases glomerular filtration
- Cellular effects: antimitogenic effects
- Hormonal:
- Inhibition of aldosterone and renin secretion and perhaps of antidiuretic hormone
- Stimulation of lipolysis.
- ANP and BNP could decrease the feeling of thirst and appetite for salt.
- It has overall opposite effects to angiotensin II.
- It has been suggested that CNP is EDHF, the endothelium-derived hyperpolarizing factor, through activation of peptide receptor subtype C (NPR-C).
Therapeutic application
Drugs with ANP-mimetic effect could be used in treatment of arterial hypertension, congestive heart failure and states of blood volume expansion.
Nesiritide, a recombinant BNP, has given good results in congestive heart failure treatment.
Inhibitors of neutral endopeptidase, by reducing natriuretic peptides inactivation, increase their concentrations and their effects. Omapatrilat, inhibitor of both neutral endopeptidase and angiotensin converting enzyme, often called vasopeptidase inhibitor, is currently studied.
Adrenomedullin
Adrenomedullin is a 52 amino acid peptide present in adrenal medulla and in other tissues, heart, kidney, intestine. Adrenomedullin has vasodilator and natriuretic effects. It is structurally similar to CGRP (calcitonin-gene related peptide).
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