Brain natriuretic peptide

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Natriuretic peptide precursor B
Identifiers
Symbols NPPB ; BNP
External IDs Template:OMIM5 HomoloGene81698
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species Human Mouse
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UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]

Synonyms and keywords: BNP; B-type natriuretic peptide; GC-B

Overview

Brain natriuretic peptide is a 32 amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of myocytes (heart muscles cells). At the time of release, a co-secreted 76 amino acid N-terminal fragment (NT-proBNP) is also released with BNP. BNP binds to and activates atrial natriuretic factor receptor (NPRA) 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. Both ANP and BNP have limited ability to bind and activate NPRB.

Historical Perspective

BNP was originally identified in extracts of porcine brain [1]. Thus the name brain natriuretic peptide. But in humans it is produced mainly in the cardiac ventricles.

Physiology

BNP is released from the ventricular myocytes as a 134 amino acid preprohormone, in response to stretch. It is further cleaved into a 76 amino acid N-terminal fragment (N-terminal BNP) and a 32 amino acid active hormone and released into the blood [2]. Animal studies have shown that BNP gene expression increases rapidly in response to ventricular stretch.[3]

Physiologic actions of BNP and ANP include:

  • Effects on heart and vessels include:
  • Effects on the kidney include:[6]
    • Increase in glomerular filtration rate
    • Increase in renal plasma flow
    • Increase in urine flow rate
    • Inhibition of distal sodium re-absorption

Thus, the resulting effect of these peptides is a decrease in blood volume, blood pressure and an increase in natriuresis.

Clinical Significance

Heart Failure

Tests showing raised levels of BNP or NT-proBNP in the blood are used in the diagnosis of heart failure and may be useful to establish prognosis in heart failure, as both markers are typically higher in patients with worse outcome.[7]

Both BNP and NT-proBNP have been approved as a marker for acute congestive heart failure (CHF). The plasma concentrations of both BNP are increased in patients with asymptomatic and symptomatic left ventricular dysfunction. However, in the emergency setting, normal levels of BNP and NT-proBNP rule out acute heart failure [8]. 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 were statistically significant. Effects on all cause hospital mortality were inconclusive.[9] The BNP test is also used for the risk stratification of patients with acute coronary syndromes.[10][11]

There is no level of BNP that perfectly separates patients with and without heart failure:[8]

  • BNP < 100 pg per milliliter:
  • BNP < 50 pg per milliliter:

For patients with CHF, 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, for which the test is considered inconclusive. Values above 500 are generally considered to be positive.

In a study to test the hypothesis that brain natriuretic peptide levels can predict cardiac mortality in diabetic patients, Bhalla et al showed that BNP appears to be a reliable predictor of future cardiac and all-cause mortality in these patients [12]. Also, BNP was found to have an important role in prognostication of heart surgery patients[13] and in the emergency department.[14] Bhalla et al. showed that combining BNP with other tools likeimpedence cardiography (ICG) can improve early diagnosis of heart failure and advance prevention strategies[15][16]. Treatment of decompensated heart failure with diuretics, vasodilators, ACE inhibitors, ARBs, beta-blockers and aldosterone antagonists can result in quick fall of BNP levels.

In summary, in the setting of an elevated BNP, careful physician evaluation and other diagnostic tests should be considered to confirm the diagnosis of heart failure and also, attention must be paid towards other causes of raised BNP.

Others

Utility of BNP has also been explored in various settings like preeclampsia, ICU and shock and end stage renal disease (ESRD).[17][18][19][20] BNP can also be elevated in renal failure (acute and chronic) (as about <5% of BNP is excreted renally) and it can be decreased in obesity [21]. Unlike BNP, NT-pro BNP is solely reliant on the kidney for excretion. Other medical conditions that can cause elevation of BNP levels include:

Studies have shown that BNP levels may be helpful in predicting response to cardiac resynchronization therapy (CRT)[23][24] and sudden death in patients with chronic heart failure and acute myocardial infarction [25].

For reasons unknown female gender and elderly age are also associated with elevated BNP levels. [26][27]

Recombinant BNP

BNP is also marketed as nesiritide, a recombinant form of the 32 amino acid human BNP, for the treatment of acute decompensated congestive heart failure.[28]

References

  1. Sudoh T, Kangawa K, Minamino N, Matsuo H (1988). "A new natriuretic peptide in porcine brain". Nature. 332 (6159): 78–81. doi:10.1038/332078a0. PMID 2964562. Unknown parameter |month= ignored (help)
  2. Mukoyama M, Nakao K, Hosoda K; et al. (1991). "Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide". The Journal of Clinical Investigation. 87 (4): 1402–12. doi:10.1172/JCI115146. PMC 295184. PMID 1849149. Unknown parameter |month= ignored (help)
  3. Hama N, Itoh H, Shirakami G; et al. (1995). "Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction". Circulation. 92 (6): 1558–64. PMID 7664440. Unknown parameter |month= ignored (help)
  4. Brunner-La Rocca HP, Kaye DM, Woods RL, Hastings J, Esler MD (2001). "Effects of intravenous brain natriuretic peptide on regional sympathetic activity in patients with chronic heart failure as compared with healthy control subjects". Journal of the American College of Cardiology. 37 (5): 1221–7. PMID 11300426. Unknown parameter |month= ignored (help)
  5. Clarkson PB, Wheeldon NM, Macleod C, Coutie W, MacDonald TM (1995). "Brain natriuretic peptide: effect on left ventricular filling patterns in healthy subjects". Clinical Science (London, England : 1979). 88 (2): 159–64. PMID 7720339. Unknown parameter |month= ignored (help)
  6. Richards AM, Crozier IG, Holmes SJ, Espiner EA, Yandle TG, Frampton C (1993). "Brain natriuretic peptide: natriuretic and endocrine effects in essential hypertension". Journal of Hypertension. 11 (2): 163–70. PMID 8385176. Unknown parameter |month= ignored (help)
  7. Bhatia V, Nayyar P, Dhindsa S (2003). "Brain natriuretic peptide in diagnosis and treatment of heart failure". J Postgrad Med. 49 (2): 182–5. PMID 12867703. Full text.
  8. 8.0 8.1 Maisel A, Krishnaswamy P, Nowak R, McCord J, Hollander J, Duc P, Omland T, Storrow A, Abraham W, Wu A, Clopton P, Steg P, Westheim A, Knudsen C, Perez A, Kazanegra R, Herrmann H, McCullough P (2002). "Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure". N Engl J Med. 347 (3): 161–7. doi:10.1056/NEJMoa020233. PMID 12124404.
  9. Lam, LL; Cameron, PA; Schneider, HG; Abramson, MJ; Müller, C; Krum, H (2010). "Meta-analysis: effect of B-type natriuretic peptide testing on clinical outcomes in patients with acute dyspnea in the emergency setting". Annals of internal medicine. 153 (11): 728–35. doi:10.1059/0003-4819-153-11-201012070-00006. PMID 21135296.
  10. Bibbins-Domingo K, Gupta R, Na B, Wu AH, Schiller NB, Whooley MA (2007). "N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease". JAMA. 297 (2): 169–76. doi:10.1001/jama.297.2.169. PMC 2848442. PMID 17213400. Unknown parameter |month= ignored (help)
  11. Fitzgerald RL, Cremo R, Gardetto N, Chiu A, Clopton P, Bhalla V, Maisel AS (2005). "Effect of nesiritide in combination with standard therapy on serum concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure". Am. Heart J. 150 (3): 471–7. doi:10.1016/j.ahj.2004.11.021. PMID 16169326. Unknown parameter |month= ignored (help)
  12. Bhalla MA, Chiang A, Epshteyn VA, Kazanegra R, Bhalla V, Clopton P, Krishnaswamy P, Morrison LK, Chiu A, Gardetto N, Mudaliar S, Edelman SV, Henry RR, Maisel AS (2004). "Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus". J. Am. Coll. Cardiol. 44 (5): 1047–52. doi:10.1016/j.jacc.2004.05.071. PMID 15337217. Unknown parameter |month= ignored (help)
  13. Hutfless R, Kazanegra R, Madani M, Bhalla MA, Tulua-Tata A, Chen A, Clopton P, James C, Chiu A, Maisel AS (2004). "Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery". J. Am. Coll. Cardiol. 43 (10): 1873–9. doi:10.1016/j.jacc.2003.12.048. PMID 15145114. Unknown parameter |month= ignored (help)
  14. Maisel A, Hollander JE, Guss D, McCullough P, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R (2004). "Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath". J. Am. Coll. Cardiol. 44 (6): 1328–33. doi:10.1016/j.jacc.2004.06.015. PMID 15364340. Unknown parameter |month= ignored (help)
  15. Bhalla V, Isakson S, Bhalla MA, Lin JP, Clopton P, Gardetto N, Maisel AS (2005). "Diagnostic ability of B-type natriuretic peptide and impedance cardiography: testing to identify left ventricular dysfunction in hypertensive patients". Am. J. Hypertens. 18 (2 Pt 2): 73S–81S. doi:10.1016/j.amjhyper.2004.11.044. PMID 15752936. Unknown parameter |month= ignored (help)
  16. Castellanos LR, Bhalla V, Isakson S, Daniels LB, Bhalla MA, Lin JP, Clopton P, Gardetto N, Hoshino M, Chiu A, Fitzgerald R, Maisel AS (2009). "B-type natriuretic peptide and impedance cardiography at the time of routine echocardiography predict subsequent heart failure events". J. Card. Fail. 15 (1): 41–7. doi:10.1016/j.cardfail.2008.09.003. PMID 19181293. Unknown parameter |month= ignored (help)
  17. Resnik JL, Hong C, Resnik R, Kazanegra R, Beede J, Bhalla V, Maisel A (2005). "Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women". Am. J. Obstet. Gynecol. 193 (2): 450–4. doi:10.1016/j.ajog.2004.12.006. PMID 16098869. Unknown parameter |month= ignored (help)
  18. Bhalla V, Bhalla MA, Maisel AS (2004). "Evolution of B-type natriuretic peptide in evaluation of intensive care unit shock". Crit. Care Med. 32 (8): 1787–9. doi:10.1097/01.CCM.0000135748.75590.54. PMID 15286561. Unknown parameter |month= ignored (help)
  19. Sheen V, Bhalla V, Tulua-Tata A, Bhalla MA, Weiss D, Chiu A, Abdeen O, Mullaney S, Maisel A (2007). "The use of B-type natriuretic peptide to assess volume status in patients with end-stage renal disease". Am. Heart J. 153 (2): 244.e1–5. doi:10.1016/j.ahj.2006.10.041. PMID 17239684. Unknown parameter |month= ignored (help)
  20. Rudiger A, Gasser S, Fischler M, Hornemann T, von Eckardstein A, Maggiorini M (2006). "Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure". Critical Care Medicine. 34 (8): 2140–4. doi:10.1097/01.CCM.0000229144.97624.90. PMID 16763507. Unknown parameter |month= ignored (help)
  21. Mehra MR, Uber PA, Park MH; et al. (2004). "Obesity and suppressed B-type natriuretic peptide levels in heart failure". Journal of the American College of Cardiology. 43 (9): 1590–5. doi:10.1016/j.jacc.2003.10.066. PMID 15120816. Unknown parameter |month= ignored (help)
  22. Morita E, Yasue H, Yoshimura M; et al. (1993). "Increased plasma levels of brain natriuretic peptide in patients with acute myocardial infarction". Circulation. 88 (1): 82–91. PMID 8319360. Unknown parameter |month= ignored (help)
  23. Lellouche N, De Diego C, Cesario DA; et al. (2007). "Usefulness of preimplantation B-type natriuretic peptide level for predicting response to cardiac resynchronization therapy". The American Journal of Cardiology. 99 (2): 242–6. doi:10.1016/j.amjcard.2006.08.018. PMID 17223426. Unknown parameter |month= ignored (help)
  24. Fruhwald FM, Fahrleitner-Pammer A, Berger R; et al. (2007). "Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony". European Heart Journal. 28 (13): 1592–7. doi:10.1093/eurheartj/ehl505. PMID 17298973. Unknown parameter |month= ignored (help)
  25. Tapanainen JM, Lindgren KS, Mäkikallio TH, Vuolteenaho O, Leppäluoto J, Huikuri HV (2004). "Natriuretic peptides as predictors of non-sudden and sudden cardiac death after acute myocardial infarction in the beta-blocking era". Journal of the American College of Cardiology. 43 (5): 757–63. doi:10.1016/j.jacc.2003.09.048. PMID 14998613. Unknown parameter |month= ignored (help)
  26. Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC (2002). "Plasma brain natriuretic peptide concentration: impact of age and gender". Journal of the American College of Cardiology. 40 (5): 976–82. PMID 12225726. Unknown parameter |month= ignored (help)
  27. Wang TJ, Larson MG, Levy D; et al. (2002). "Impact of age and sex on plasma natriuretic peptide levels in healthy adults". The American Journal of Cardiology. 90 (3): 254–8. PMID 12127613. Unknown parameter |month= ignored (help)
  28. Bibbins-Domingo K, Gupta R, Na B, Wu A H B, Schiller N B, Whooley M A (2007). "N-Terminal Fragment of the Prohormone Brain-Type Natriuretic Peptide (NT-proBNP), Cardiovascular Events, and Mortality in Patients With Stable Coronary Heart Disease". 297 (2): 169–176. PMID 17213400. Unknown parameter |jornal= ignored (help) JAMA Abstract.

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. 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.
  • 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.
  • 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. PMID 16594987.
  • 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. PMID 1309330.
  • 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. PMID 2136732.
  • 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. PMID 2138890.
  • 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. PMID 2522777.
  • 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. PMID 2597152.
  • 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. PMID 7601467.
  • 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. PMID 7901875.
  • 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. PMID 8837222.
  • 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. PMID 8890728.
  • 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.
  • 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.
  • 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. PMID 11750283.
  • 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. PMID 11999635.
  • 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. PMID 12015190.
  • 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. PMID 12084525.

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