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