Natriuretic Peptide System

Ri 黃敬淳 /P 柯文哲
 History
 1981, de Bold et al. first reported a potent diuret
ic 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 at
ria
 Some is produced by ventricular tis
sue of fetus, neonate and hypertro
phy
 Increased atrial-wall tension, incre
ased intravascular volume, is the d
ominant stimulus for its release
 Several hormons and neurotransmi
tters directly stimulate the secretio
n 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 pit
uitary, kidney, vascular , an
d endothelial cells
 Believed to be an endotheli
al derived peptide participat
ing in an autocrine/paracrin
e 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 hor

mone
• Alternative processing of the AN
P precursor in the kidney
• Intrarenal paracrine regulator of
sodium and water homeostasis
• Secreted into the distal nephron
to exerts its effects in the medull
ary collecting duct
Most effects of the NPs are mediated through binding to NP receptors, which activate particu
late 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 an
Lower the activation threshold o d vasocontriction
f vagal afferent

Suppress the release

of catecholamine from
Dampen baroreceptors autonamic nerve endin
g
 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 ductBlock sodium absorption

Promote sodium and water excretion

Central Nervous System Effects

The actions of natriuretic peptides in brain r

einforce those in the periphery

• Inhibit salt appetite and water drinking

• Inhibit the secretion of vasopressin 、 corticotropi
n
• Act in the brain stem to decrease sympathetic ton
e
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 fibro

sis
•Limit the myocardial porliferative or hypertrophic respons
e 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 hig
h-pressure baro
ceptors

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 secondar
y 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 t
he 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 a
ccurate diagnosis
 The best clinical predictor of congestive heart fai
lure was as increased heart size on chest X-ray
(accuracy, 81 ％ )
 Followed by a history of congestive heart failure
What about
(accuracy, 75 ％ ) BNP?
 Rales found on physical examination (accuracy,
What is the best
69 ％ )
cut-point?
 History of paroxysmal nocturnal dyspnea (accura
cy, 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 themse
lves were more accurate than any other fi
nding in the history, physical finding, or la
boratory 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 cariova

scular 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 s
etting of cardiac surgery
Clinical application
 Prevention of cardiac remodeling of BNP
• Age
• Renal dysfunction BNP level ↑

• Women
• Obese BNP level ↓