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Atrial natriuretic peptide

For other uses, see ANP.

pressure from aortic stenosis) or injury (e.g. myocardial


infarction).

Atrial natriuretic peptide (ANP), atrial natriuretic ANP is secreted in response to:
factor (ANF), atrial natriuretic hormone (ANH),
Cardionatrine, Cardiodilatine (CDD) or atriopeptin,
Atrial distention, stretching of the vessel walls[1]
is a powerful vasodilator, and a protein (polypeptide)
hormone secreted by heart muscle cells.[1][2][3] It is in Sympathetic stimulation of -adrenoceptors
volved in the homeostatic control of body water, sodium,
Raised sodium concentration (hypernatremia),
potassium and fat (adipose tissue). It is released by musthough sodium concentration is not the direct
cle cells in the upper chambers (atria) of the heart (atrial
stimulus for increased ANP secretion[1]
myocytes) in response to high blood volume. ANP acts to
reduce the water, sodium and adipose loads on the circu Angiotensin-II
latory system, thereby reducing blood pressure.[1] ANP
has exactly the opposite function of the aldosterone se Endothelin, a potent vasoconstrictor
creted by the zona glomerulosa in regard to its eect on
sodium in the kidney that is, aldosterone stimulates
The atria become distended by high extracellular uid and
sodium retention and ANP generates sodium loss.[4][5]
blood volume, and atrial brillation. It should be noted
that ANP secretion increases in response to immersion
of the body in water, which causes atrial stretch due to
1 Structure
an altered distribution of intravascular uid. ANP secretion in response to exercise has also been demonstrated
ANP is a 28-amino acid peptide with a 17-amino acid in horses.[7]
ring in the middle of the molecule. The ring is formed ANP is also produced by the placenta in pregnant women.
by a disulde bond between two cysteine residues at posi- The exact function of this remains unclear. [8]
tions 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 Kingston, Ontario, Canada, 3 Receptors
led by Adolfo J. de Bold after they made the seminal observation that injection of atrial (but not ventricular) tis- Three types of atrial natriuretic peptide receptors have
sue extracts into rats caused copious natriuresis.[6]
been identied on which natriuretic peptides act. They
are all cell surface receptors and are designated:

Production

guanylyl cyclase-A (GC-A) also known as natriuretic peptide receptor-A (NPRA/ANPA) or NPR1

The ANP gene has 3 exons and 2 introns; it codes 151amino acid preproANP. Cleaving the 25-amino acid Nterminal results in pro-ANP. Corin, a membrane serine
protease, cleaves the nal ANP, the 28-amino acid Cterminal.

guanylyl cyclase-B (GC-B) also known as natriuretic


peptide receptor-B (NPRB/ANPB) or NPR2
natriuretic
peptide
(NPRC/ANPC) or NPR3

ANP is produced, stored, and released mainly by cardiac


myocytes of the atria of the heart. Synthesis of ANP also
takes place in the ventricles, brain, suprarenal glands, and
renal glands. It is released in response to atrial stretch
and a variety of other signals induced by hypervolemia,
exercise, or caloric restriction.[1] The hormone is constitutively expressed in the ventricles in response to stress
induced by increased afterload (e.g. increased ventricular

clearance

receptor

NPR-A and NPR-B have a single membrane-spanning


segment with an extracellular domain that binds the
ligand. The intracellular domain maintains two consensus
catalytic domains for guanylyl cyclase activity. Binding
of a natriuretic peptide induces a conformational change
in the receptor that causes receptor dimerization and activation. Thus, binding of ANP to its receptor causes
1

the conversion of GTP to cGMP and raises intracellular cGMP. As a consequence, cGMP activates a cGMPdependent kinase (PKG or cGK) that phosphorylates proteins at specic serine and threonine residues. In the
medullary collecting duct, the cGMP generated in response to ANP may act not only through PKG but also
via direct modulation of ion channels.[9] NPR-C functions mainly as a clearance receptor by binding and sequestering ANP from the circulation. All natriuretic peptides are bound by the NPR-C. Atrial natriuretic peptide
and brain natriuretic peptide bind and activate GC-A,
whereas CNP binds and activates GC-B.[10]

OTHER NATRIURETIC FACTORS

4.3 Vascular
Relaxes vascular smooth muscle in arterioles and venules
by:
Membrane Receptor-mediated elevation of vascular
smooth muscle cGMP
Inhibition of the eects of catecholamines

4.4 Cardiac
Inhibits maladaptive cardiac hypertrophy

Physiological eects

Mice lacking cardiac NPRA develop increased cardiac mass and severe brosis and die suddenly[13]

Re-expression of NPRA rescues the phenotype.


ANP binds to a specic set of receptors ANP receptors.
Receptor-agonist binding causes a reduction in blood vol[14]
ume and, therefore, a reduction in cardiac output and sys- It may be associated with isolated atrial amyloidosis.
temic blood pressure. Lipolysis is increased and renal
sodium reabsorption is decreased. The overall eect of
4.5 Adipose tissue
ANP on the body is to counter increases in blood pressure
and volume caused by the renin-angiotensin system.
Increases the release of free fatty acids from adipose
tissue. Plasma concentrations of glycerol and nonesteried fatty acids are increased by i.v. infusion of
ANP in humans.
4.1 Renal
Dilates the aerent glomerular arteriole, constricts the eerent glomerular arteriole, and relaxes the mesangial cells. This increases pressure
in the glomerular capillaries, thus increasing the
glomerular ltration rate (GFR), resulting in greater
excretion of sodium and water.
Increases blood ow through the vasa recta, which
will wash the solutes (NaCl and urea) out of the
medullary interstitium.[11] The lower osmolarity of
the medullary interstitium leads to less reabsorption
of tubular uid and increased excretion.
Decreases sodium reabsorption in the distal convoluted tubule (interaction with NCC)[12] and cortical
collecting duct of the nephron via guanosine 3',5'cyclic monophosphate (cGMP) dependent phosphorylation of ENaC
Inhibits renin secretion, thereby inhibiting the reninangiotensin-aldosterone system.

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

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

6 Other natriuretic factors

In addition to the mammalian natriuretic peptides (ANP,


BNP, CNP), other natriuretic peptides with similar struc4.2 Adrenal
ture and properties have been isolated elsewhere in the
animal kingdom. Tervonen (1998) described a salmon
Reduces aldosterone secretion by the zona glomeru- natriuretic peptide known as salmon cardiac peptide,[15]
losa of the adrenal cortex.
while dendroaspis natriuretic peptide (DNP) can be

3
found in the venom of the green mamba, a species of
African snake.[16]

Pharmacological modulation

[8] http://www.biolreprod.org/content/54/4/834.full.pdf
[9] Mohler ER, Finkbeiner WE (2011). Medical Physiology
(Boron) (2 ed.). Philadelphia: Saunders. ISBN 1-43771753-5.
[10] Mkikallio, Kaarin (2002). ANP. Placental insuciency and fetal heart: Doppler ultrasonographic
and biochemical markers of fetal cardiac dysfunction.
Oulu: Oulun yliopisto. ISBN 951-42-6737-0. OCLC
58358685.

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 [11] Kiberd BA, Larson TS, Robertson CR, Jamison RL (June
1987). Eect of atrial natriuretic peptide on vasa recta
NEP and angiotensin-converting enzyme) developed by
blood ow in the rat. Am. J. Physiol. 252 (6 Pt 2):
BMS did not receive FDA approval due to angioedema
F11127. PMID 2954471.
safety concerns. Other dual inhibitors of NEP with
ACE/angiotensin receptor are currently being developed [12] Reeves WB, Andreoli TE (2008). Chapter 31
by pharmaceutical companies.[17]
Sodium Chloride Transport in the Loop of Henle,

See also
Atrial volume receptors
Brain natriuretic peptide
C-type natriuretic peptide

References

[1] Widmaier, Eric P.; Hershel Ra; Kevin T. Strang (2008).


Vanders Human Physiology, 11th Ed. McGraw-Hill. pp.
291, 50910. ISBN 978-0-07-304962-5.
[2] Potter LR, Yoder AR, Flora DR, Antos LK, Dickey
DM (2009). Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handb Exp Pharmacol. Handbook of Experimental Pharmacology 191 (191): 34166. doi:10.1007/9783-540-68964-5_15. ISBN 978-3-540-68960-7. PMID
19089336.

Distal Convoluted Tubule, and Collecting Duct. In


Giebisch GH, Alpern RA, Herbert SC, Seldin, DW.
Seldin and Giebischs the kidney: physiology and pathophysiology.
Amsterdam: Elsevier/Academic Press.
doi:10.1016/B978-012088488-9.50034-6. ISBN 0-12088488-7.
[13] Kong X, Wang X, Hellermann G, Lockey RF, Mohapatra
S (2007). Mice Decient in Atrial Natriuretic Peptide
Receptor A (NPRA) Exhibit Decreased Lung Inammation: Implication of NPRA Signaling in As`thma Pathogenesis. The Journal of Allergy and Clinical Immunology
119 (1): S127. doi:10.1016/j.jaci.2006.11.482.
[14] Rcken C, Peters B, Juenemann G, Saeger W, Klein
HU, Huth C, Roessner A, Goette A (October 2002).
Atrial amyloidosis: an arrhythmogenic substrate for persistent atrial brillation. Circulation 106 (16): 2091
7. doi:10.1161/01.CIR.0000034511.06350.DF. PMID
12379579.
[15] Tervonen V, Arjamaa O, Kokkonen K, Ruskoaho H,
Vuolteenaho O (September 1998).
A novel cardiac hormone related to A-, B- and C-type natriuretic peptides. Endocrinology 139 (9): 40215.
doi:10.1210/en.139.9.4021. PMID 9724061.

[3] Addicks K, Forssmann WG, Henkel H, Holthausen U,


Menz V, Rippegather G, Ziskoven D (1989). Calciumcalmodulin antagonists Inuences the release of cardiodilatin/ANP from atrial cardiocytes. In Wambach G, Kaufmann W. Endocrinology of the heart. Berlin: SpringerVerlag. ISBN 0-387-51409-0.

[16] Schweitz H, Vigne P, Moinier D, Frelin C, Lazdunski M


(July 1992). A new member of the natriuretic peptide
family is present in the venom of the green mamba (Dendroaspis angusticeps)". J Biol Chem. 267 (20): 13928
32. PMID 1352773.

[4] Goetz KL (1988). Physiology and pathophysiology of


atrial peptides. Am. J. Physiol. 254 (1 Pt 1): E115.
PMID 2962513.

[17] Venugopal J (2003).


Pharmacological modulation of the natriuretic peptide system.
Expert
Opinion on Therapeutic Patents 13 (9):
1389.
doi:10.1517/13543776.13.9.1389.

[5] Hoehn K, Marieb EN (2013). 16. Human anatomy &


physiology (9th ed.). Boston: Pearson. p. 629. ISBN
978-0-321-74326-8. question number 14
[6] de Bold AJ (1985). Atrial natriuretic factor: a hormone
produced by the heart. Science 230 (4727): 76770.
doi:10.1126/science.2932797. PMID 2932797.
[7] Kokkonen, Ulla-Maija (2002). Plasma Atrial Natriuretic
peptides in the horse and goat with special reference to
exercising horses.

10 External links
Atrial Natriuretic Factor at the US National Library
of Medicine Medical Subject Headings (MeSH)

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