Brain natriuretic peptide

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Natriuretic peptide precursor B
Identifiers
Symbols	NPPB; BNP
External IDs	OMIM: 600295 HomoloGene: 81698 GeneCards: NPPB Gene
Gene Ontology Molecular function • diuretic hormone activity Cellular component • extracellular region • extracellular space Biological process • cell surface receptor linked signal transduction • fluid secretion • blood pressure regulation • negative regulation of angiogenesis • diuresis • natriuresis • negative regulation of cell growth • regulation of vasodilation • regulation of vascular permeability • regulation of blood vessel size Sources: Amigo / EGO
RNA expression pattern
250px
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4879	n/a
Ensembl	ENSG00000120937	n/a
UniProt	P16860	n/a
RefSeq (mRNA)	NM_002521	n/a
RefSeq (protein)	NP_002512	n/a
Location (UCSC)	Chr 1: 11.84 - 11.84 Mb	n/a
PubMed search	[1]	n/a

Brain natriuretic peptide (BNP), now known as B-type natriuretic peptide (also BNP) or GC-B, is a 32 amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of heart muscle cells (cardiomyocytes). BNP is named as such because it was originally identified in extracts of porcine brain, although in humans it is produced mainly in the cardiac ventricles.

BNP is co-secreted along with a 76 amino acid N-terminal fragment (NT-proBNP) which is biologically inactive. BNP binds to and activates the atrial natriuretic factor receptors 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, 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 ANP and include decrease in systemic vascular resistance and central venous pressure as well as an increase in natriuresis. Thus, the net effect of BNP and ANP is a decrease in blood volume and a decrease in cardiac output.

Clinical significance

Both BNP and NT-proBNP levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure, as both markers are typically higher in patients with worse outcome. The plasma concentrations of both BNP and NT-proBNP are also typically increased in patients with asymptomatic or symptomatic left ventricular dysfunction. There is no level of BNP that perfectly separates patients with and without heart failure. BNP accurately reflects current ventricular status The half-life of NT-ProBNP is 1 to 2 hours vs. 20 minutes for BNP.

BNP > 100 pg per milliliter

• sensitivity = 90%
• specificity = 76%

BNP > 50 pg per milliliter

• sensitivity = 97%
• specificity = 62%

For patients with CHF, BNP values will generally be above 100 pg per milliliter; however, a more conservative interpretation of the BNP is that normal values are less than 50 pg per milliliter in order to achieve adequate sensitivity. There is a diagnostic 'gray area', often defined as between 100 and 500 pg/mL, for which the test is considered inconclusive. Values above 500 pg/mL are generally considered to be positive. 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.

Bhalla et al. showed that BNP plays a very important role in prognostication of millions of diabetics. Also BNP has 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.

NT-proBNP levels (in pg/mL) by NYHA functional class

	NYHA I	NYHA II	NYHA III	NYHA IV
5th Percentile	33	103	126	148
Mean	1015	1666	3029	3465
95th Percentile	3410	6567	10,449	12,188

BNP can be elevated in renal failureBNP is cleared by binding to natriuretic peptide receptors (NPRs) and neutral endopeptidase (NEP) Less than 5% of BNP is cleared renally. NTproBNP is the inactive molecule resulting from cleavage of the prohormone Pro-BNP and is SOLELY reliant 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.

The BNP test is used as an aid in the diagnosis and assessment of severity of congestive heart failure (also referred to as heart failure). The BNP test is also used for the risk stratification of patients with acute coronary syndromes.

When interpreting an elevated BNP level, it is useful to remember that values may be elevated due to factors other than heart failure. Higher levels are often seen in obese patients and those with renal disease, in the absence of heart failure.

BNP is also one of the reasons why people will feel the need to urinate after getting into the bathtub or pool. The increased pressure on the body drives more fluid back into systemic circulation which in turn leads to a slight increase in preload. The left ventricle, and to a small degree the left atrium, secrete BNP in response. The natriuretic effect of BNP leads to an increase in urine production.

See also

• Atrial natriuretic peptide
• C-type natriuretic peptide

Further reading

• Cosson S (2004). "Usefulness of B-type natriuretic peptide (BNP) as a screen for left ventricular abnormalities in diabetes mellitus". Diabetes Metab. 30 (4): 381–6. doi:10.1016/S1262-3636(07)70132-5. PMID 15525883. 
• Cauliez B, Berthe MC, Lavoinne A (2005). "[Brain natriuretic peptide: physiological, biological and clinical aspects]". Ann. Biol. Clin. (Paris). 63 (1): 15–25. PMID 15689309. CS1 maint: Multiple names: authors list (link)
• Buchner S, Riegger G, Luchner A (2005). "[Clinical utility of the cardiac markers BNP and NT-proBNP]". Acta Med. Austriaca. 31 (4): 144–51. PMID 15732251. CS1 maint: Multiple names: authors list (link)
• LaPointe MC (2005). "Molecular regulation of the brain natriuretic peptide gene". Peptides. 26 (6): 944–56. doi:10.1016/j.peptides.2004.08.028. PMID 15911064. 
• Hoffmann U, Borggrefe M, Brueckmann M (2006). "New horizons: NT-proBNP for risk stratification of patients with shock in the intensive care unit". Critical care (London, England). 10 (2): 134. doi:10.1186/cc4883. PMC 1550883 Freely accessible. PMID 16594987. CS1 maint: Multiple names: authors list (link)
• Suga S, Nakao K, Hosoda K; et al. (1992). "Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide". Endocrinology. 130 (1): 229–39. doi:10.1210/en.130.1.229. PMID 1309330. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kambayashi Y, Nakao K, Mukoyama M; et al. (1990). "Isolation and sequence determination of human brain natriuretic peptide in human atrium". FEBS Lett. 259 (2): 341–5. doi:10.1016/0014-5793(90)80043-I. PMID 2136732. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Hino J, Tateyama H, Minamino N; et al. (1990). "Isolation and identification of human brain natriuretic peptides in cardiac atrium". Biochem. Biophys. Res. Commun. 167 (2): 693–700. doi:10.1016/0006-291X(90)92081-A. PMID 2138890. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Sudoh T, Maekawa K, Kojima M; et al. (1989). "Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide". Biochem. Biophys. Res. Commun. 159 (3): 1427–34. doi:10.1016/0006-291X(89)92269-9. PMID 2522777. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Seilhamer JJ, Arfsten A, Miller JA; et al. (1990). "Human and canine gene homologs of porcine brain natriuretic peptide". Biochem. Biophys. Res. Commun. 165 (2): 650–8. doi:10.1016/S0006-291X(89)80015-4. PMID 2597152. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Arden KC, Viars CS, Weiss S; et al. (1995). "Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome 1p36". Genomics. 26 (2): 385–9. doi:10.1016/0888-7543(95)80225-B. PMID 7601467. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Weir ML, Pang SC, Flynn TG (1993). "Characterization of binding sites in rat for A, B and C-type natriuretic peptides". Regul. Pept. 47 (3): 291–305. doi:10.1016/0167-0115(93)90396-P. PMID 7901875. CS1 maint: Multiple names: authors list (link)
• Totsune K, Takahashi K, Satoh F; et al. (1996). "Urinary immunoreactive brain natriuretic peptide in patients with renal disease". Regul. Pept. 63 (2-3): 141–7. doi:10.1016/0167-0115(96)00035-3. PMID 8837222. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Totsune K, Takahashi K, Murakami O; et al. (1996). "Immunoreactive brain natriuretic peptide in human adrenal glands and adrenal tumors". Eur. J. Endocrinol. 135 (3): 352–6. doi:10.1530/eje.0.1350352. PMID 8890728. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Matsuo K, Nishikimi T, Yutani C; et al. (1999). "Diagnostic value of plasma levels of brain natriuretic peptide in arrhythmogenic right ventricular dysplasia". Circulation. 98 (22): 2433–40. PMID 9832489. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Wiese S, Breyer T, Dragu A; et al. (2001). "Gene expression of brain natriuretic peptide in isolated atrial and ventricular human myocardium: influence of angiotensin II and diastolic fiber length". Circulation. 102 (25): 3074–9. PMID 11120697. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Shimizu H, Masuta K, Aono K; et al. (2002). "Molecular forms of human brain natriuretic peptide in plasma". Clin. Chim. Acta. 316 (1-2): 129–35. doi:10.1016/S0009-8981(01)00745-8. PMID 11750283. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ogawa K, Oida A, Sugimura H; et al. (2002). "Clinical significance of blood brain natriuretic peptide level measurement in the detection of heart disease in untreated outpatients: comparison of electrocardiography, chest radiography and echocardiography". Circ. J. 66 (2): 122–6. doi:10.1253/circj.66.122. PMID 11999635. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Asakawa H, Fukui T, Tokunaga K, Kawakami F (2002). "Plasma brain natriuretic peptide levels in normotensive Type 2 diabetic patients without cardiac disease and macroalbuminuria". J. Diabetes Complicat. 16 (3): 209–13. doi:10.1016/S1056-8727(01)00173-8. PMID 12015190. CS1 maint: Multiple names: authors list (link)
• Bordenave L, Georges A, Bareille R; et al. (2003). "Human bone marrow endothelial cells: a new identified source of B-type natriuretic peptide". Peptides. 23 (5): 935–40. doi:10.1016/S0196-9781(02)00004-9. PMID 12084525. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

External links

• MeSH Brain+Natriuretic+Peptide

de:Brain Natriuretic Peptide sv:Brain natriuretic peptide