Download Atrial Natriuretic Peptides

Atrial Natriuretic
Peptides [ANP]
9th of February, 2017
Atrial Natriuretic Peptides
Overview...1/4
 Cardiac natriuretic peptides are an important
family of mediators
 Atrial Natriuretic Factor (ANF) is a 28 amino
acid polypeptide hormone secreted mainly by the
heart atria in response to atrial stretch
 ANF acts on the kidney to increase sodium
excretion and GFR, to antagonize renal
vasoconstriction, and to inhibit renin secretion
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Atrial Natriuretic Peptides
Overview...2/4
 Atrial natriuretic peptide (ANP), atrial
natriuretic factor (ANF), atrial natriuretic
hormone (ANH), Cardionatrine,
Cardiodilatine (CDD) or atriopeptin, is a
powerful vasodilator, and a protein
(polypeptide) hormone secreted by heart
muscle cells.
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Atrial Natriuretic Peptides
Overview...3/4
 It is involved in the homeostatic control of body
water, sodium, potassium and fat (adipose
tissue).
 It is released by muscle cells in the upper
chambers (atria) of the heart (atrial myocytes) in
response to high blood pressure.
 ANP acts to reduce the water, sodium and
adipose loads on the circulatory system, thereby
reducing blood pressure.
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Atrial Natriuretic Peptides
Overview...4/4
 ANP has exactly the opposite function of the
aldosterone secreted by the zona
glomerulosa in regard to its effect on sodium
in the kidney –that is, aldosterone stimulates
sodium retention and ANP generates sodium
loss
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Atrial Natriuretic Peptides
Learning Objectives
 At the end of the session, students should
1)
2)
3)
4)
be able to understand and describe the
following:Nature and biosynthesis
Main effects
Mechanism of action
Therapeutic potential
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Atrial Natriuretic Peptides –
1) Nature and Biosynthesis...1/3
 Atrial cells have a specialised endocrine function
in relation to the cardiovascular system
 They contain secretory granules, and store and
release atrial natriuretic peptide (ANP) with
powerful effects on the kidney and vascular
system
 Release of ANP occurs during volume overload in
response to stretching of the atria, and
 intravenous saline infusion is sufficient to
stimulate its release.
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Atrial Natriuretic Peptides –
1) Nature and Biosynthesis...2/3
 Two related natriuretic peptides (B and C) are
found
 B-natriuretic peptide (BNP) is released from
ventricular muscle and opposes ventricular
fibrosis.
 The plasma concentration of B-type natriuretic
peptide (BNP) is predictably increased in
patients with heart failure and is increasingly
used as an aid to diagnosis.
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Atrial Natriuretic Peptides –
1) Nature and Biosynthesis...3/3
 C-natriuretic peptide (CNP) is stored in
vascular endothelium
 in addition to vascular actions influences
development of long bones.
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Atrial Natriuretic Peptides –
2) Main Effects
 To increase Na+ and water excretion by the
kidney
 Relax vascular smooth muscle (except efferent
arterioles of renal glomeruli)
 Increase vascular permeability
 Inhibit the release and/or actions of several
hormones and mediators including aldosterone,
angiotensin II, endothelin and antidiuretic
hormone (ADH)
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Atrial Natriuretic Peptides –
3) Mechanism of Action...1/4
 ANPs exert their action by combining with
membrane receptors (natriuretic peptide
receptors, NPRs) which exist at least in two
subtypes designated (A and B)
 Both NPR-A and NPR-B incorporate a catalytic
guanylate cyclase moiety (refer to How drugs act:
molecular aspects)
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Atrial Natriuretic Peptides –
Mechanism of Action...2/4
 ANP-receptor binding leads to increase cGMP
(cyclic 3’5’-guanosine monophosphate)
intracellular generation, same response as that
produced by organic nitrates and endothelialderived-NO (nitric oxide)
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Atrial Natriuretic Peptides –
Mechanism of Action...3/4
 However, interaction is through membrane-
bound guanylate cyclase for ANP and soluble
guanylate cyclase for organic nitrates and
endothelial NO
 Renal glomerular afferent arterioles are
dilated by ANP but efferent arterioles are
constricted, increasing filtration pressure
leading to increased glomerular filtration and
enhanced Na+ excretion
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Atrial Natriuretic Peptides –
Mechanism of Action...4/4
 Elsewhere, natriuretic peptides cause
vasodilatation (vasorelaxation) and
reduce blood pressure
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Atrial Natriuretic peptides –
4) Therapeutic Potential
 Vasodilations leads to decreased cardiac load
(pre- and afterload)
 Increase Na+ and water excretion leads to
reduction in preload
 For example: Nesiritide, a recombinant form of
human B-type natriuretic peptide (BNP) approved
by the FDA for the treatment of acute heart failure
syndromes
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 However, a pooled analysis of randomised
controlled trials has suggested that it too may
increase mortality
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Reference
 Rang & Dale Pharmacology Textbook, 7th Ed,
p 252-253
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