Natriuretic Peptide System
Ri 黃敬淳/P 柯文哲
History
1981, de Bold et al. first reported a potent
diuretic and natriuretic factor in rat atrial
extracts
1984, Kangawa et al. identified atrial natriuretic
peptide (ANP)
1988, B-type or brain natriuretic peptide (BNP)
1990, C-type natriuretic peptide (CNP)
Natriuretic peptide family: ANP, BNP, CNP,
DNP(dendroaspis), Urodilatin
Shares a common 17-amino acid disulfide ring
Molecular biology - ANP
28 a.a peptide hormone
Produced primarily in the cardiac
atria
Some is produced by ventricular
tissue of fetus, neonate and
hypertrophy
Increased atrial-wall tension,
increased intravascular volume, is
the dominant stimulus for its
release
Several hormons and
neurotransmitters directly stimulate
the secretion of ANP
Molecular biology - BNP
32 a.a peptide hormone
Initially isolated from
porcine brain
Primarily derived from the
cardiac ventricle
Secreted primarily in
response to increasing
cardiac wall tension
ANP- burst- acute change of atrial pressure
BNP- gene- chronically increased pressure
Curr Probl Cardiol, December 2004
Molecular biology - CNP
22 a.a peptide hormone
Predominates in the central
nervous system, anterior
pituitary, kidney, vascular ,
and endothelial cells
Believed to be an
endothelial derived peptide
participating in an
autocrine/paracrine role to
regulate vascular
structure and tone
Molecular biology – DNP, Urodilatin
DNP: 38 a.a peptide hormone
First isolated from the venom of
the green mamba snake
Physiologic role in unclear
• Urodilatin: 32 a.a peptide
hormone
• Alternative processing of the
ANP precursor in the kidney
• Intrarenal paracrine regulator of
sodium and water homeostasis
• Secreted into the distal nephron
to exerts its effects in the
medullary collecting duct
Most effects of the NPs are mediated through binding to NP receptors, which activate
particulate guanylyl cyclase and produce the second messenger, cyclic guanosine
monophosphate (cGMP)
The New England Journal of medicine Volume 339 Number 5, 1998
Cardiovascular Effects
•Increase venous capacitance
•Promotes natriuresis in kidney Reduce cardiac preload
•Suppresion of RAA system
Reflex tachycardia
Lower the activation threshold and vasocontriction
of vagal afferent
Suppress the release
of catecholamine from
Dampen baroreceptors autonamic nerve
ending
Renal Effects
1. Afferent renal arteriole relaxation
GFR ↑
2. Efferent renal arteriole constriction
3. Relax mesangial cell surface area ↑
4. Production of Urodilatin paracrine effect
5. Proximal tubule Inhibit angiotensin Ⅱ
6. Cortical collecting duct Antagonize vasopression
7. Medullary collecting ductBlock sodium absorption
Promote sodium and water excretion
Central Nervous System Effects
The actions of natriuretic peptides in brain
reinforce those in the periphery
• Inhibit salt appetite and water drinking
• Inhibit the secretion of vasopressin、corticotropin
• Act in the brain stem to decrease sympathetic
tone
The New England Journal of medicine Volume 339 Number 5, 1998
Anti-Remodeling Effects
•Inhibit the growth of cardiac fibroblast
•Retard the deposition of collage
•Induce cardiac myocyte aptosis
•Inhibit transforming growth factor (TGF-β) induced
fibrosis
•Limit the myocardial porliferative or hypertrophic
response to injury or ischemia
Anti-remodeling and Anti-fibrotic properties
NPs
NTG
•Randomized study in 60 patients with first anterior myocardial infarction
•Present with TIMI grade 0 or 1 by coronary angiography
•Prolong chest pain (>30min)+ ST elevation (>2mV, > 2 precordial leads) + successful infused (>24 hr.)
•Then all give ACEI(enalapril)
•Repeat cardiac catheterization one month later
Journal of the American College of Cardiology Vol. 37, No. 7, 2001
Clinical application of BNP in the
emergency diagnosis of heart
failure
Unloading of
high-pressure
baroceptors
The New England Journal of medicine August 19, 1998
Response of NPs to heart failure
1. Myocardial failure with hypertrophy
2. Stretching of the failing atrial and ventricular myocardium
3. Elevated plasma concentration of Angiotensin Ⅱ
Increased production of BNP 、 ANP
1. Catecholamines ↓ The concentrations are
2. Anigotensin Ⅱ ↓ correlated with the
3. Aldosterone ↓ extent of ventricular
4. Systemic vascular resistance ↓ dysfunction
5. Systemic volume ↓
Myocardial performace ↑
110±225 pg/ml
346±390 pg/ml
675±450 pg/ml
1. Total of 1586 p’t from seven sites enrolled from April 1999 ~ December 2000
2. Came to the emergency department with acute dyspnea
3. Exclude patient under 18 y/o, those whose dyspnea was clearly not
secondary to CHF, and those with AMI or renal failure
4. BNP was measured
5. The CHF was diagnosed by two independent cardiologists who were blind to
the result of BNP
The New England Journal of medicine Volume 347 July 18, 2002
The New England Journal of medicine Volume 347 July 18, 2002
Predictors of Congestive Heart Failure
A major challenge of heart failure is timely and
accurate diagnosis
The best clinical predictor of congestive heart
failure was as increased heart size on chest X-
ray (accuracy, 81％)
Followed by a history of congestive
What heart
about failure
BNP?
(accuracy, 75％)
What is the best
Rales found on physical examination (accuracy,
69％) cut-point?
History of paroxysmal nocturnal dyspnea
(accuracy, 60％)
The New England Journal of medicine Volume 347 July 18, 2002
The New England Journal of medicine Volume 347 July 18, 2002
Cardiovasc Rev Rep 25(3):100-104, 2004
Thank You For Your Attension!!
Conclusion
B-type natriuretic peptide levels by
themselves were more accurate than any
other finding in the history, physical
finding, or laboratory value in delineating
the cause of dyspnea
CLEVELAND CLINIC JOURNAL OF MEDICINE
VOLUME 70 • NUMBER 4 APRIL 2003
Heart failure When dose BNP
Pulmonary hypertension increase?
Atherosclertic vascular disease
Biomarker in patient with heart failure and other
cariovascular diasease
Early warning system to help to identify patients at high
risk for cardiac events
Recombinant ANP (carperitide) and BNP (nesiritide) are
useful for management of acutely decompensated HF
Investigated for myocardial and renal protection in the
setting of cardiac surgery
Clinical application of
Prevention of cardiac remodeling BNP
• Age
• Renal dysfunction BNP level ↑
• Women
• Obese BNP level ↓
