Atrial Natriuretic Peptide

Information about Atrial Natriuretic Peptide

natriuretic peptide precursor A
Identifiers
Symbol	NPPA
Alt. Symbols	ANP, PND
Entrez	4878
HUGO	7939
OMIM	108780
RefSeq	NM_006172
UniProt	P01160
Other data
Locus	Chr. 1 p36.21

Atrial natriuretic peptide (ANP), atrial natriuretic factor (ANF), or atriopeptin, is a polypeptide hormone involved in the homeostatic control of body water, sodium, and adiposity. It is released by atrial myocytes, muscle cells in the atria of the heart, in response to high blood pressure. ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood pressure.

Structure

ANP is a 28 amino acid peptide with a 17 amino acid ring in the middle of the molecule. The ring is formed by a disulfide bond between two cysteine residues at positions 7 and 23. ANP is closely related to BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide) which all share the same amino acid ring. ANP was discovered in 1981 by a team in Ottawa led by Adolfo J. de Bold after they made the seminal observation that injection of atrial (but not ventricular) tissue extracts into rats caused copious natriuresis.^[1]

Production

ANP is produced, stored and released by atrial myocytes, muscle cells in the atria of the heart. It is released in response to a variety of signals induced by hypervolaemia, exercise or caloric restriction. The hormone is constitutively expressed in the ventricle in response to stress induced by increased afterload (eg. increased ventricular pressure from aortic stenosis) or injury (eg. myocardial infarction).

ANP is secreted in response to:

Atrial distention, stretching of the vessel walls
Sympathetic stimulation of β-adrenoceptors
Raised sodium concentration (hypernatremia)
Angiotensin-II
Endothelin, a potent vasoconstrictor

The atria become distended by high extracellular fluid and blood volume, and atrial fibrillation. Notably, ANP secretion increases in response to immersion of the body in water, which causes atrial stretch due to an altered distribution of intravascular fluid. ANP secretion in response to exercise has also been demonstrated in horses.

Physiological effects

ANP binds to a specific set of receptors. Receptor-agonist binding causes a reduction in blood volume and therefore a reduction in cardiac output and systemic blood pressure. Lipolysis and renal sodium secretion and excretion are also increased. The overall effect of ANP on the body is to counter increases in blood pressure and volume caused by the renin-angiotensin system.

Renal

Dilates the afferent glomerular arteriole, constricts the efferent glomerular arteriole, and relaxes the mesangial cells. This increases pressure in the glomerular capillaries, thus increasing the glomerular filtration rate (GFR), resulting in greater excretion of sodium and water.
Decreases sodium reabsorption in the proximal convoluted tubule and cortical collecting duct of the nephron via guanosine 3',5'-cyclic monophosphate (cGMP) dependant phosphorylation of ENaC
Inhibits renin secretion, thereby inhibiting the renin-angiotensin system.
Reduces aldosterone secretion by the adrenal cortex.

Vascular

Relaxes vascular smooth muscle in arterioles and venules by:
Receptor-mediated elevation of vascular smooth muscle cGMP
Inhibition of the effects of catecholamines

Cardiac

Inhibits maladaptive cardiac hypertrophy
Mice lacking cardiac NPRA develop increased cardiac mass and severe fibrosis and die suddenly
Re-expression of NPRA rescues the phenotype.

Adipose tissue

Increases the release of free fatty acids from adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
Activates adipocyte plasma membrane type A guanylyl cyclase receptors NPR-A
Increases intracellular cGMP levels that induce the phosphorylation of a hormone-sensitive lipase and perilipin A via the activation of a cGMP dependent protein kinase-I cGK-I
Does not modulate cAMP production or PKA activity

Degradation

Mediation of the effects of ANP is achieved through gradual degradation of the peptide by the enzyme neutral endopeptidase (NEP). Recently NEP inhibitors have been developed, although they have not yet been licensed. They may be clinically useful in treating congestive heart disease.

Other natriuretic factors

In addition to the mammalian natriuretic peptides (ANP, BNP, CNP), two others have been isolated. Tervonen (1998) described a salmon natriuretic peptide, named Salmon cardiac peptide, with similar structure and properties^[2]. As well, Dendroaspis Natriuretic Peptide (DNP) was discovered in the venom of the green mamba by Schweitz et al. (1992).

Diagnostic Use

Used in conjunction with other clinical information, measurement of B-type natriuretic peptide (BNP) can help determine whether a patient's dyspnea is caused by congestive heart failure in which BNP levels are elevated. This laboratory test has become a valuable and quick method for diagnostic work-up of patients presenting to the emergency department (ED) with acute dyspnea.

Pharmacological modulation

Neutral endopeptidase (NEP)is the enzyme that metabolizes natriuretic peptides. Several inhibitors of NEP are currently being developed to treat disorders ranging from hypertension to heart failure. Most of them are dual inhibitors. Omapatrilat (dual inhibitor of NEP and Angiotensin Converting Enzyme) developed by BMS did not receive FDA approval due to angioedema safety concerns. Other dual inhibitors of NEP with ACE / angiotensin receptor are currently being developed by pharmaceutical companies.^[3]

References

1. ^ de Bold A (1985). "Atrial natriuretic factor: a hormone produced by the heart.". Science 230 (4727): 767-70. PMID 2932797.
2. ^ Tervonen et al., 1998 Endocrinology 139:4021-4025.
3. ^ [1] Joshi Venugopal. (2003) Pharmacological modulation of the natriuretic peptide system. Expert Opinion on Therapeutic Patents 13:9, 1389

External links

MeSH Atrial+Natriuretic+Factor

• • [ e] Endocrine system: hormones/endocrine glands (Peptide hormones, Steroid hormones)
Hypothalamic-pituitary	Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α (FSH, LH, TSH), GH, prolactin, POMC (ACTH, MSH, endorphins, lipotropin)
Adrenal axis	Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA
Thyroid axis	Thyroid: thyroid hormone (T₃ and T₄) - calcitonin - Parathyroid: PTH
Gonadal axis	Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin (pregnancy)
Other end. glands	Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin
Non-end. glands	Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Liver/other: Insulin-like growth factor (IGF-1, IGF-2)
Target-derived	NGF, BDNF, NT-3

• • [ e] Urinary system, physiology: renal physiology and acid base physiology
Filtration	Ultrafiltration - Countercurrent exchange
Hormones affecting filtration	Antidiuretic hormone (ADH) - Aldosterone - Atrial natriuretic peptide
Endocrine	Renin - Erythropoietin (EPO) - Calcitriol (Active vitamin D) - Prostaglandins
Assessing Renal function / Measures of dialysis	Glomerular filtration rate - Creatinine clearance - Renal clearance ratio - Urea reduction ratio - Kt/V - Standardized Kt/V - Hemodialysis product
Acid base physiology	Fluid balance - Darrow Yannet diagram - Body water - Interstitial fluid - Extracellular fluid - Intracellular fluid/Cytosol - Plasma - Transcellular fluid - Base excess - Davenport diagram - Anion gap
Buffering/compensation	Bicarbonate buffering system - Respiratory compensation - Renal compensation

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locus (plural loci) is a fixed position on a chromosome, such as the position of a gene or a biomarker (genetic marker). A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map.
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Peptides (from the Greek πεπτίδια, "small digestibles") are short polymers formed from the linking, in a defined order, of α-amino acids.
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hormone (from Greek όρμή - "to set in motion") is a chemical messenger that carries a signal from one cell (or group of cells) to another. All multicellular organisms produce hormones (including plants - see phytohormone).
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Homeostasis is the property of either an open system or a closed system, especially a living organism, to regulate the state of its internal environment so as to maintain a stable, constant condition.
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Water is a common chemical substance that is essential to all known forms of life.^[1] In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor.
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Sodium (IPA: /ˈsəʊdiəm/) is a chemical element which has the symbol Na (Latin: natrium), atomic number 11, atomic mass 22.9898 g/mol, common oxidation number +1.
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muscle fiber, also spelled muscle fibre (see spelling differences), also technically known as a myocyte, is a single cell of a muscle. Muscle fibers contain many myofibrils, the contractile unit of muscles.
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In anatomy, the atrium (plural: atria) refers to a chamber or space. As such it may for example be the atrium of the lateral ventricle in the brain or, popularly, the blood collection chamber of a heart.
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Cysteine (abbreviated as Cys or C)^[1] is an α-amino acid with the chemical formula HO₂CCH(NH₂)CH₂SH. It is not an essential amino acid, which means that humans can synthesize it. Its codons are UGU and UGC.
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Brain natriuretic peptide (also known as B-type natriuretic peptide or "GC-B") is a 32 amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of myocytes (heart muscles cells) in the ventricles.
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C-type Natriuretic peptide (CNP)is a 22 amino acid peptide that has strong vasorelaxant properties. Unlike ANP and BNP, CNP does not have direct natriuretic activity. This is due to the fact that CNP is a selective agonist for the B-type Natriuretic receptor (NPRB) whereas ANP and
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19th century - 20th century - 21st century
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1978 1979 1980 - 1981 - 1982 1983 1984

Year 1981 (MCMLXXXI
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The Sympathetic Nervous System (SNS) is a branch of the autonomic nervous system. It is always active at a basal level (called sympathetic tone) and becomes more active during times of stress.
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adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines. Adrenergic receptors specifically bind their endogenous ligands, the catecholamines adrenaline and noradrenaline (called epinephrine and norepinephrine
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Hypernatremia is an electrolyte disturbance consisting of an elevated sodium level in the blood (compare to hyponatremia, meaning a low sodium level). The most common cause of hypernatremia is not an excess of sodium, but a relative deficit of free water in the body.
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Angiotensin is an oligopeptide in the blood that causes vasoconstriction, increased blood pressure, and release of aldosterone from the adrenal cortex. It is a powerful dipsogen. It is derived from the precursor molecule angiotensinogen, a serum globulin produced in the liver.
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Identifiers
Symbol EDN2

Entrez 1907
HUGO 3177
OMIM 131241

RefSeq NM_001956
UniProt P20800
Other data

Locus Chr. 1 p34 Endothelin is a 21-amino acid vasoconstricting peptide that plays a key part in vascular homeostasis.
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A vasoconstrictor, also vasopressor or simply pressor, is any substance that acts to cause vasoconstriction (narrowing of the lumena of blood vessels) and usually results in an increase of the blood pressure.
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Atrial fibrillation
Classification & external resources

The P waves, which represent depolarization of the atria, are irregular or absent during atrial fibrillation.
ICD-10 I 48.
ICD-9 427.
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There are three distinct atrial natriuretic factor receptors identified so far in mammals, natriuretic peptide receptors A, B and C (NPRA or NPR1 , NPRB or NPR2 and NPRAC or NPR3 ).
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agonist is a substance that binds to a specific receptor and triggers a response in the cell. It mimics the action of an endogenous ligand (such as hormone or neurotransmitter) that binds to the same receptor.
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Lipolysis is the breakdown of fat stored in fat cells. During this process, free fatty acids are released into the bloodstream and circulate throughout the body. Ketones are produced, and are found in large quantities in ketosis (an adaptive metabolic state that occurs when
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The kidneys are organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. The medical field that studies the kidneys and diseases of the kidney is called nephrology^[1].
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The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system (RAAS) is a hormone system that helps regulate long-term blood pressure and extracellular volume in the body.
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