Brain natriuretic peptide 32 (BNP), also known as B-type natriuretic peptide, is a
hormone secreted by
cardiomyocytes in the
heart ventricles in response to stretching caused by increased ventricular blood volume. Along with
NT-proBNP
The N-terminal prohormone of brain natriuretic peptide (NT-proBNP or BNPT) is a prohormone with a 76 amino acid N-terminal inactive protein that is cleaved from the molecule to release brain natriuretic peptide.
Both BNP and NT-proBNP levels in ...
, BNP is one of two natriuretic peptides.
The 32-amino acid polypeptide BNP is secreted attached to a 76–amino acid
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
fragment in the
prohormone called
NT-proBNP
The N-terminal prohormone of brain natriuretic peptide (NT-proBNP or BNPT) is a prohormone with a 76 amino acid N-terminal inactive protein that is cleaved from the molecule to release brain natriuretic peptide.
Both BNP and NT-proBNP levels in ...
(BNPT), which is biologically inactive. Once released, BNP binds to and activates the
atrial natriuretic factor receptor NPRA, and to a lesser extent
NPRB, in a fashion similar to
atrial natriuretic peptide (ANP) but with 10-fold lower affinity. The
biological half-life of BNP, however, is twice as long as that of
ANP ANP may refer to:
In politics and government
*Afghan National Police
*''Agência Nacional do Petróleo, Gás Natural e Biocombustíveis'' or National Agency of Petroleum, Natural Gas and Biofuels (Brazil), a regulatory agency in Brazil
*American N ...
, and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing.
The physiologic actions of BNP are similar to those of ANP and include decrease in
systemic
Systemic fundamental to a predominant social, economic, or political practice. This refers to:
In medicine
In medicine, ''systemic'' means affecting the whole body, or at least multiple organ systems. It is in contrast with ''topical'' or ''loc ...
vascular resistance and
central venous pressure as well as an increase in
natriuresis. The net effect of these peptides is a decrease in blood pressure due to the decrease in systemic vascular resistance and, thus, afterload. Additionally, the actions of both BNP and ANP result in a decrease in cardiac output due to an overall decrease in central venous pressure and preload as a result of the reduction in blood volume that follows natriuresis and diuresis.
Biosynthesis
BNP is synthesized as a 134-amino acid preprohormone (preproBNP), encoded by the human gene NPPB. Removal of the 25-residue N-terminal signal peptide generates the prohormone, proBNP, which is stored intracellularly as an O-linked
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
; proBNP is subsequently cleaved between arginine-102 and serine-103 by a specific convertase (probably
furin or
corin) into NT-proBNP and the biologically active 32-amino acid polypeptide BNP-32, which are secreted into the blood in equimolar amounts.
Cleavage at other sites produces shorter BNP peptides with unknown biological activity.
Processing of proBNP may be regulated by O-glycosylation of residues near the cleavage sites.
Physiologic effects
Since the actions of BNP are mediated via the ANP receptors, the physiologic effects of BNP are identical to those of ANP, those will be reviewed here.
Receptor-
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
binding causes a reduction in
renal sodium reabsorption Renal reabsorption of sodium ( Na+) is a part of renal physiology. It uses Na-H antiport, Na-glucose symport, sodium ion channels (minor). , which results in a decreased blood volume. Secondary effects may be an improvement in cardiac
ejection fraction and reduction of systemic blood pressure.
Lipolysis is also increased.
Renal
* Dilates the afferent glomerular arteriole, constricts the efferent glomerular arteriole, and relaxes the
mesangial cells. This increases pressure in the
glomerular capillaries, thus increasing the
glomerular filtration rate (GFR), resulting in greater filter load of sodium and water.
* Increases blood flow through the vasa recta, which will wash the solutes (NaCl and urea) out of the medullary interstitium.
The lower osmolarity of the medullary interstitium leads to less reabsorption of tubular fluid and increased excretion.
* Decreases sodium reabsorption in the
distal convoluted tubule (interaction with
NCC NCC may refer to:
Biology
*Neural correlates of consciousness, neuronal events and mechanisms relating to perception phenomena
*Sodium-chloride symporter, abbreviated as NCC
Companies
*National Certification Corporation, a nursing specialty cer ...
)
and
cortical collecting duct of the
nephron via guanosine 3',5'-cyclic monophosphate (
cGMP CGMP is an initialism. It can refer to:
*cyclic guanosine monophosphate (cGMP)
*current good manufacturing practice (cGMP)
*CGMP, Cisco Group Management Protocol, the Cisco version of Internet Group Management Protocol
The Internet Group Managem ...
) dependent phosphorylation of
ENaC.
* Inhibits
renin secretion, thereby inhibiting the
renin–angiotensin–aldosterone system.
Adrenal
* Reduces aldosterone secretion by the zona glomerulosa of the
adrenal cortex
The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is ...
.
Vascular
Relaxes vascular smooth muscle in arterioles and venules by:
* Membrane Receptor-mediated elevation of vascular smooth muscle cGMP
* Inhibition of the effects of catecholamines
Promotes uterine spiral artery remodeling, which is important for preventing pregnancy-induced hypertension.
Cardiac
* Inhibits maladaptive cardiac hypertrophy
* Mice lacking cardiac NPRA develop increased cardiac mass and severe fibrosis and die suddenly
* Re-expression of NPRA rescues the phenotype.
Adipose tissue
* Increases the release of
free fatty acids from adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
* 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
cGMP-dependent protein kinase or protein kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP. It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle ...
-I (cGK-I)
* Does not modulate
cAMP production or
PKA
PKA may refer to:
* Professionally known as:
** Pen name
** Stage persona
* p''K''a, the symbol for the acid dissociation constant at logarithmic scale
* Protein kinase A, a class of cAMP-dependent enzymes
* Pi Kappa Alpha, the North-American so ...
activity
Measurement
BNP and NT-proBNP are measured by
immunoassay.
Interpretation of BNP
* The main clinical utility of either BNP or NT-proBNP is that a normal level helps to rule out chronic heart failure in the emergency setting. An elevated BNP or NT-proBNP should never be used exclusively to "rule in" acute or chronic heart failure in the emergency setting due to lack of specificity .
* Either BNP or NT-proBNP can also be used for screening and prognosis of heart failure.
* BNP and NT-proBNP are also typically increased in patients with left ventricular dysfunction, with or without symptoms (BNP accurately reflects current ventricular status, as its half-life is 20 minutes, as opposed to 1–2 hours for NT-proBNP).
A preoperative BNP can be predictive of a risk of an acute cardiac event during vascular surgery. A
cutoff of 100 pg/ml has a
sensitivity
Sensitivity may refer to:
Science and technology Natural sciences
* Sensitivity (physiology), the ability of an organism or organ to respond to external stimuli
** Sensory processing sensitivity in humans
* Sensitivity and specificity, statisti ...
of approximately 100%, a
negative predictive value
The positive and negative predictive values (PPV and NPV respectively) are the proportions of positive and negative results in statistics and diagnostic tests that are true positive and true negative results, respectively. The PPV and NPV descr ...
of approximately 100%, a
specificity of 90%, and a
positive predictive value
The positive and negative predictive values (PPV and NPV respectively) are the proportions of positive and negative results in statistics and diagnostic tests that are true positive and true negative results, respectively. The PPV and NPV descr ...
of 78% according to data from the
United Kingdom.
BNP is cleared by binding to natriuretic peptide receptors (NPRs) and neutral endopeptidase (NEP). Less than 5% of BNP is cleared renally. NT-proBNP is the inactive molecule resulting from cleavage of the prohormone Pro-BNP and is reliant solely on the kidney for excretion. The ''achilles heel'' of the NT-proBNP molecule is the overlap in kidney disease in the heart failure patient population.
Some laboratories report in units ng per Litre (ng/L), which is equivalent to pg/mL
There is a diagnostic 'gray area', often defined as between 100 and 500 pg/mL, for which the test is considered inconclusive, but, in general, levels above 500 pg/ml are considered to be an indicator of heart failure. This so-called gray zone has been addressed in several studies, and using clinical history or other available simple tools can help make the diagnosis.
BNP has been suggested as a predictor for a variety of
medical states, including cardiovascular mortality in diabetics
and cardiac impairment in cancer patients.
BNP was found to have an important role in prognostication of heart surgery patients
and in the emergency department.
Bhalla et al. showed that combining BNP with other tools like ICG can improve early diagnosis of heart failure and advance prevention strategies.
Utility of BNP has also been explored in various settings like preeclampsia, ICU and shock and ESRD.
The effect or race and gender on value of BNP and its utility in that context has been studied extensively.
The BNP test is used as an aid in the diagnosis and assessment of severity of heart failure. A recent meta-analysis concerning effects of BNP testing on clinical outcomes of patients presenting to the emergency department with acute dyspnea revealed that BNP testing led to a decrease in admission rates and decrease in mean length of stay, although neither was statistically significant. Effects on all cause hospital mortality was inconclusive.
The BNP test is also used for the risk stratification of patients with acute coronary syndromes.
When interpreting an elevated BNP level, values may be elevated due to factors other than heart failure. Lower levels are often seen in obese patients.
Higher levels are seen in those with renal disease, in the absence of heart failure.
Therapeutic application
Recombinant BNP,
nesiritide, has been suggested as a treatment for decompensated heart failure. However, a clinical trial failed to show a benefit of nesiritide in patients with
acute decompensated heart failure.
Blockade of
neprilysin, a protease known to degrade members of the natriuretic peptide family, has also been suggested as a possible treatment for heart failure. Dual administration of neprilysin inhibitors and
angiotensin receptor blockers has been shown to be advantageous to
ACE inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...
s, the current first-line therapy, in multiple settings.
See also
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References
Further reading
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External links
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* BNP and NT-proBNP a
Lab Tests Online*
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{{Nerve tissue protein
''attribution'': copied from
Brain natriuretic peptide version as of 13:57, 4 December 2019
Cardiology
Genes on human chromosome 1
Hormones