Polypeptide secreted by atrial cells when the atrium is distended.
Secreted in response to signals from myocardial stretch and volume overload.
Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that is encoded by the NPPA gene.
Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/paracrine factors that are structurally related.
The main function of ANP is causing a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion.
It is synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart.
These cardiac wall cells contain volume receptors which respond to increased stretching of the atrial wall due to increased atrial blood volume.
Reduction of blood volume by ANP can result in secondary effects such as reduction of extracellular fluid (ECF) volume, improved cardiac ejection fraction with resultant improved organ perfusion, decreased blood pressure, and increased serum potassium.
These effects may be diminished or negated by various counter-regulatory mechanisms operating concurrently on each of these secondary effects.
Brain natriuretic peptide (BNP) –is secreted by cardiac muscle cells in the heart ventricles – is similar to ANP in its effect.
It acts via the same receptors as ANP does, but with 10-fold lower affinity than ANP.
The biological half-life of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better choices than ANP for diagnostic blood testing.
ANP carries out endocrine functions of the heart, acting as a diuretic by inhibiting sodium reabsorption in the kidneys.
ANP also acts in the heart to prevent cardiac hypertrophy and to regulate vascular remodeling and energy metabolism.
Fetal expression of NPPA is associated with the formation of chamber myocardium, muscle cells of the atria and ventricles in the early developing heart.
Early expression of this gene has been associated with ventricular hypertrophy in both in vitro and in vivo models.
NPPA gene variants affect plasma ANP concentrations, blood pressure levels, and cardiovascular diseases such as atrial fibrillation (AF).
These findings suggest NPPA gene is a critical in cardiac development and dysfunction of this gene can lead to heart problems via altered ANP levels.
ANP is a 28-amino acid peptide with a 17-amino acid ring in the middle of the molecule.
ANP is closely related to BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide), which all share a similar amino acid ring structure.
ANP is one of a family of nine structurally similar natriuretic hormones: seven are atrial in origin.
ANP is synthesized as an inactive preprohormone, encoded by the human NPPA gene located on the short arm of chromosome 1.
The NPPA gene is expressed primarily in atrial myocytes.
It consists of 2 introns and three exons, yielding a high molecular mass 151 amino acid polypeptide known as preproANP.
The preprohormone cleavage of the 25 amino acid signal sequence to produce proANP, a 126 amino acid peptide that is the major form of ANP stored in intracellular granules of the atria.
Following stimulation of atrial cells, proANP is released and rapidly converted to mature ANP on the cell surface.
ANP is secreted in response to the:
Stretching of the atrial wall, by atrial volume receptors
Increases in sympathetic stimulation of β-adrenoceptors.
Increased sodium concentration with hypernatremia, though sodium concentration is not the direct stimulus for increased ANP secretion
Three types of atrial natriuretic peptide receptors have been identified on which natriuretic peptides act.
The binding of ANP to its receptor causes the conversion of GTP to cGMP to raise intracellular cGMP.
Natriuretic peptide receptor C functions mainly as a clearance receptor by binding and sequestering ANP from the circulation.
All natriuretic peptides are bound by the NPR-C.
Maintenance of the ECF volume and its subcompartment the vascular space, is essential for survival.
The ECF and vascular space are maintained in a narrow range, despite the presence of marked variation in dietary sodium intake.
Three volume regulating systems: two salt saving systems, the renin angiotensin aldosterone system (RAAS) and the renal sympathetic system (RSS); and the salt excreting natriuretic peptide (NP) hormone system.
When the vascular space contracts, the RAAS and RSS are activated, and when the atria expand, NP’s are “turned on”. Each system also suppresses its counteracting system(s). NP’s are made in cardiac, intestinal, renal, and adrenal tissue.
ANP in one of a family of cardiac NP’s: others at BNP, CNP, and DNP.
ANP binds to a specific set of receptors, ANP receptors.
Receptor-agonist binding causes the increase in renal sodium excretion, which results in a decreased ECF and blood volume.
Secondary effects may be an improvement in cardiac ejection fraction and reduction of systemic blood pressure.
ANP acts on the kidney to increase sodium and water excretion (natriuresis) in the following ways:
The medullary collecting duct is the main site of ANP regulation of sodium excretion.
ANP inhibits ENaC on the apical side and the sodium potassium ATPase pump resulting in less sodium re-absorption and more sodium excretion.
ANP increases glomerular filtration rate and glomerular permeability.
ANP directly dilates the afferent arteriole, counteracting the norepinephrine induced vasoconstriction of the afferent arteriole.
ANP inhibits the effect of Angiotensin II on the mesangial cells, and increases the radius and number of glomerular pores, thereby increasing glomerular permeability and resulting in greater filter load of sodium and water.
Increases blood flow through the vasa recta.
It inhibits renin secretion, thereby inhibiting the production of angiotensin and aldosterone.
It inhibits the renal sympathetic nervous system.
ANP has the opposite effect of angiotensin II on the kidney: angiotensin II increases renal sodium retention and ANP increases renal sodium loss.
It reduces aldosterone secretion by the zona glomerulosa of the adrenal cortex, and relaxes vascular smooth muscle in arterioles and venules.
ANP inhibits cardiac hypertrophy in heart failure as well as fibrosis, by preventing fibroblasts from entering heart tissue and replicating, as well as decreasing inflammation.
ANP prevents hypertrophy by inhibiting calcium influx that is caused by norepinephrine.
ANP Increases the release of free fatty acids from adipose tissue.
ANP is produced locally by several immune cells.
ANP regulates several functions of innate and adaptive immune system as well as shown to have cytoprotective effects.
ANP modulates innate immunity by raising defense against extracellular microbes.
ANP inhibits the release of pro-inflammatory markers and expression of adhesion molecules.
There is evidence of cytoprotective effects of ANP in myocardial, vascular smooth, endothelial, hepatocytes and tumor cells.
Modulation of the effects of ANP occurs through degradation of the peptide by the enzyme neutral endopeptidase (NEP).
Neutral endopeptidase (NEP) inhibitors have been developed, such as Sacubitril and Sacubitril/valsartan that is useful in treating patients in heart failure with reduced ejection fraction .
Fragments derived from the ANP precursor, include the signal peptide, N-terminal pro-ANP and ANP, have been detected in human blood.
ANP and related peptides are used as biomarkers for cardiovascular diseases such as stroke, coronary artery disease, myocardial infarction and heart failure.
Large amounts of ANP secretion has been noted to cause electrolyte disturbances: hyponatremia and polyuria.
These indications can be a marker of a large atrial myxoma.
Brain natriuretic peptide (BNP) – is a misnomer.
BNP is secreted by ventricular myocytes – is similar to ANP in its effect.
It acts via atrial natriuretic peptide receptors but with 10-fold lower affinity than ANP.
The biological half-life of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better choices than ANP for diagnostic blood testing.
Five additional natriuretic peptides have been identified: long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide, urodilatin, and adrenomedullin. Produced with its inactive amino terminal fragment NT-proANP.
Can produce vasodilation, natriuresis and diuresis during hypertension and congestive heart failure.
Inhibits renin and aldosterone secretion, sympathetic nervous system, cardiac fibrosis and hypertrophy, and improves diastolic function and introduces metabolic protective properties along with BNP.
Atrial distention due to volume expansion with saline, water immersion, postural changes, and salt intake resulting in an increased plasma atrial natriuretic peptide.
Has no predictive value for cardiovascular mortality or morbidity.
Increased circulating volume is the most important stimulant of ANP release.
Other factors increasing ANP release include endothelin, platelet activating factor, corticotropin-releasing factor, and glucagon like peptide-1 can trigger the synthesis of ANP.
ANP is synthesized as a 151 amino acid pre-pro hormone and is stored in atrial myocytes as a 126 amino acid pro hormone (pro-ANP).
When secreted, pro-AN P is cleaved yielding N-ANP and active C-terminal hormone ANP.