Brain natriuretic peptide: Difference between revisions

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__NOTOC__
{{Infobox_gene}}
{{PBB_Controls
'''Brain natriuretic peptide''' ('''BNP'''), also known as '''B-type natriuretic peptide''', is a [[hormone]] secreted by [[cardiomyocytes]] in the [[Ventricle (heart) |heart ventricles]] in response to stretching caused by increased ventricular blood volume. BNP is named as such because it was originally identified in extracts of [[pig]] brain.
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{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Natriuretic peptide precursor B
| HGNCid = 7940
| Symbol = NPPB
  | AltSymbols =; BNP
| OMIM = 600295
| ECnumber = 
| Homologene = 81698
| MGIid = 
| GeneAtlas_image1 = PBB_GE_NPPB_206801_at_tn.png
| Function = {{GNF_GO|id=GO:0008613 |text = diuretic hormone activity}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}}
| Process = {{GNF_GO|id=GO:0007166 |text = cell surface receptor linked signal transduction}} {{GNF_GO|id=GO:0007589 |text = fluid secretion}} {{GNF_GO|id=GO:0008217 |text = blood pressure regulation}} {{GNF_GO|id=GO:0016525 |text = negative regulation of angiogenesis}} {{GNF_GO|id=GO:0030146 |text = diuresis}} {{GNF_GO|id=GO:0030147 |text = natriuresis}} {{GNF_GO|id=GO:0030308 |text = negative regulation of cell growth}} {{GNF_GO|id=GO:0042312 |text = regulation of vasodilation}} {{GNF_GO|id=GO:0043114 |text = regulation of vascular permeability}} {{GNF_GO|id=GO:0050880 |text = regulation of blood vessel size}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 4879
    | Hs_Ensembl = ENSG00000120937
    | Hs_RefseqProtein = NP_002512
    | Hs_RefseqmRNA = NM_002521
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 11840108
    | Hs_GenLoc_end = 11841575
    | Hs_Uniprot = P16860
    | Mm_EntrezGene = 
    | Mm_Ensembl = 
    | Mm_RefseqmRNA = 
    | Mm_RefseqProtein = 
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 
    | Mm_GenLoc_start = 
    | Mm_GenLoc_end = 
    | Mm_Uniprot = 
  }}
}}
{{SI}}
{{CMG}}; {{AE}} {{RT}}


{{SK}} BNP; B-type natriuretic peptide; GC-B
The 32-amino acid polypeptide BNP is secreted attached to a 76–amino acid [[N-terminus|N-terminal]] fragment in the [[prohormone]] called [[N-terminal prohormone of brain natriuretic peptide|NT-proBNP]] (BNPT), which is biologically inactive. Once released, BNP binds to and activates the [[atrial natriuretic factor receptor]] [[Atrial natriuretic factor receptor|NPRA]], and to a lesser extent [[Atrial natriuretic factor receptor|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 [[Atrial natriuretic peptide|ANP]], and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing.


==Overview==
The physiologic actions of BNP are similar to those of ANP and include decrease in [[systemic circulation|systemic]] [[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.<ref>{{cite web|url=http://cvpharmacology.com/diuretic/natriuretics|title=CV Pharmacology - Natriuretic Peptides|author=|date=|website=cvpharmacology.com|accessdate=29 April 2018|deadurl=no|archiveurl=https://web.archive.org/web/20171021200256/http://cvpharmacology.com/diuretic/natriuretics|archivedate=21 October 2017|df=}}</ref>
Brain natriuretic peptide is a 32 amino acid polypeptide secreted by the [[Ventricle (heart)|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 [[Atrial natriuretic peptide|ANP]]. Both ANP and BNP have limited ability to bind and activate [[Atrial natriuretic factor receptor|NPRB]].


==Historical Perspective==
== Biosynthesis ==
BNP was originally identified in extracts of porcine brain <ref name="pmid2964562">{{cite journal |author=Sudoh T, Kangawa K, Minamino N, Matsuo H |title=A new natriuretic peptide in porcine brain |journal=[[Nature]] |volume=332 |issue=6159 |pages=78–81 |year=1988 |month=March |pmid=2964562 |doi=10.1038/332078a0 |url=}}</ref>. Thus the name brain natriuretic peptide. But in humans it is produced mainly in the cardiac ventricles.


==Physiology==
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]]; 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.<ref name="pmid16750161">{{cite journal |vauthors=Schellenberger U, O'Rear J, Guzzetta A, Jue RA, Protter AA, Pollitt NS | title = The precursor to B-type natriuretic peptide is an O-linked glycoprotein | journal = Arch. Biochem. Biophys. | volume = 451 | issue = 2 | pages = 160–6 |date=July 2006 | pmid = 16750161 | doi = 10.1016/j.abb.2006.03.028 }}</ref> Cleavage at other sites produces shorter BNP peptides with unknown biological activity.<ref name="pmid19808300">{{cite journal |vauthors=Niederkofler EE, Kiernan UA, O'Rear J, Menon S, Saghir S, Protter AA, Nelson RW, Schellenberger U | title = Detection of endogenous B-type natriuretic peptide at very low concentrations in patients with heart failure | journal = Circ Heart Fail | volume = 1 | issue = 4 | pages = 258–64 |date=November 2008 | pmid = 19808300 | doi = 10.1161/CIRCHEARTFAILURE.108.790774 }}</ref> Processing of proBNP may be regulated by O-glycosylation of residues near the cleavage sites.<ref name="pmid19168558">{{cite journal |vauthors=Semenov AG, Postnikov AB, Tamm NN, Seferian KR, Karpova NS, Bloshchitsyna MN, Koshkina EV, Krasnoselsky MI, Serebryanaya DV, Katrukha AG | title = Processing of pro-brain natriuretic peptide is suppressed by O-glycosylation in the region close to the cleavage site | journal = Clin. Chem. | volume = 55 | issue = 3 | pages = 489–98 |date=March 2009 | pmid = 19168558 | doi = 10.1373/clinchem.2008.113373 }}</ref>
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 <ref name="pmid1849149">{{cite journal |author=Mukoyama M, Nakao K, Hosoda K, ''et al.'' |title=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 |journal=[[The Journal of Clinical Investigation]] |volume=87 |issue=4 |pages=1402–12 |year=1991 |month=April |pmid=1849149 |pmc=295184 |doi=10.1172/JCI115146 |url=}}</ref>.  Animal studies have shown that BNP gene expression increases rapidly in response to ventricular stretch.<ref name="pmid7664440">{{cite journal |author=Hama N, Itoh H, Shirakami G, ''et al.'' |title=Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction |journal=[[Circulation]] |volume=92 |issue=6 |pages=1558–64 |year=1995 |month=September |pmid=7664440 |doi= |url=}}</ref>


Physiologic actions of BNP and ANP include:
==Physiologic effects==
* Effects on heart and vessels include:
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.
** Inhibition of cardiac sympathetic activity<ref name="pmid11300426">{{cite journal |author=Brunner-La Rocca HP, Kaye DM, Woods RL, Hastings J, Esler MD |title=Effects of intravenous brain natriuretic peptide on regional sympathetic activity in patients with chronic heart failure as compared with healthy control subjects |journal=[[Journal of the American College of Cardiology]] |volume=37 |issue=5 |pages=1221–7 |year=2001 |month=April |pmid=11300426 |doi= |url=}}</ref>
** Decrease in [[systemic circulation|systemic]] [[vascular resistance]]<ref name="pmid7720339">{{cite journal |author=Clarkson PB, Wheeldon NM, Macleod C, Coutie W, MacDonald TM |title=Brain natriuretic peptide: effect on left ventricular filling patterns in healthy subjects |journal=[[Clinical Science (London, England : 1979)]] |volume=88 |issue=2 |pages=159–64 |year=1995 |month=February |pmid=7720339 |doi= |url=}}</ref>
** Decrease in central venous pressure
* Effects on the kidney include:<ref name="pmid8385176">{{cite journal |author=Richards AM, Crozier IG, Holmes SJ, Espiner EA, Yandle TG, Frampton C |title=Brain natriuretic peptide: natriuretic and endocrine effects in essential hypertension |journal=[[Journal of Hypertension]] |volume=11 |issue=2 |pages=163–70 |year=1993 |month=February |pmid=8385176 |doi= |url=}}</ref>
** 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]].
Receptor-[[agonist]] binding causes a reduction in [[renal sodium reabsorption]], 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.


==Clinical Significance==
=== Renal ===
===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.<ref>{{cite journal | author = Bhatia V, Nayyar P, Dhindsa S | title = Brain natriuretic peptide in diagnosis and treatment of heart failure. | journal = J Postgrad Med | volume = 49 | issue = 2 | pages = 182-5 | year = 2003 | id = PMID 12867703}} ''[http://www.jpgmonline.com/article.asp?issn=0022-3859;year=2003;volume=49;issue=2;spage=182;epage=5;aulast=Bhatia Full text].''</ref>


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. In the emergency setting, normal levels of BNP and NT-proBNP rule out acute heart failure <ref name="pmid12124404">{{cite journal |author=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 |title=Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure |journal=N Engl J Med |volume=347 |issue=3 |pages=161–7 |year=2002 |doi=10.1056/NEJMoa020233|pmid=12124404}}</ref>. 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.<ref>{{cite journal|pmid=21135296|year=2010|last1=Lam|first1=LL|last2=Cameron|first2=PA|last3=Schneider|first3=HG|last4=Abramson|first4=MJ|last5=Müller|first5=C|last6=Krum|first6=H|title=Meta-analysis: effect of B-type natriuretic peptide testing on clinical outcomes in patients with acute dyspnea in the emergency setting|volume=153|issue=11|pages=728–35|doi=10.1059/0003-4819-153-11-201012070-00006|journal=Annals of internal medicine}}</ref> The BNP test is also used for the risk stratification of patients with [[acute coronary syndrome]]s.<ref name="pmid17213400">{{cite journal | author = Bibbins-Domingo K, Gupta R, Na B, Wu AH, Schiller NB, Whooley MA | title = N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease | journal = JAMA | volume = 297 | issue = 2 | pages = 169–76 | year = 2007 | month = January | pmid = 17213400 | doi = 10.1001/jama.297.2.169 | url = | pmc = 2848442  }}</ref><ref name="pmid16169326">{{cite journal | author = Fitzgerald RL, Cremo R, Gardetto N, Chiu A, Clopton P, Bhalla V, Maisel AS | title = Effect of nesiritide in combination with standard therapy on serum concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure | journal = Am. Heart J. | volume = 150 | issue = 3 | pages = 471–7 | year = 2005 | month = September | pmid = 16169326 | doi = 10.1016/j.ahj.2004.11.021 | url =  }}</ref>
* Dilates the afferent glomerular arteriole, constricts the efferent glomerular arteriole, and relaxes the [[mesangial cell]]s. This increases pressure in the [[glomerulus|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.<ref name="pmid2954471">{{cite journal | vauthors = Kiberd BA, Larson TS, Robertson CR, Jamison RL | title = Effect of atrial natriuretic peptide on vasa recta blood flow in the rat | journal = The American Journal of Physiology | volume = 252 | issue = 6 Pt 2 | pages = F1112–7 | date = Jun 1987 | pmid = 2954471 | doi = | url = http://ajprenal.physiology.org/cgi/content/abstract/252/6/F1112 | deadurl = yes | archiveurl = https://web.archive.org/web/20090108133007/http://ajprenal.physiology.org/cgi/content/abstract/252/6/F1112# | archivedate = 2009-01-08 | df = | access-date = 2017-09-09 }}</ref> 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 [[Sodium-chloride symporter|NCC]])<ref name="isbn0-12-088488-7">{{cite book |vauthors=Reeves WB, Andreoli TE | veditors = Giebisch GH, Alpern RA, Herbert SC, Seldin DW | title = Seldin and Giebisch's the kidney: physiology and pathophysiology | publisher = Elsevier/Academic Press | location = Amsterdam | year = 2008 | pages = | isbn = 0-12-088488-7 | chapter = Chapter 31 – Sodium Chloride Transport in the Loop of Henle, Distal Convoluted Tubule, and Collecting Duct | doi = 10.1016/B978-012088488-9.50034-6 }}</ref> and [[cortical collecting duct]] of the [[nephron]] via guanosine 3',5'-cyclic monophosphate ([[cyclic guanosine monophosphate|cGMP]]) dependent phosphorylation of [[epithelial sodium channel|ENaC]].
* Its natriuretic effect is affected by [[dopamine]] and [[dopamine receptor D1|dopamine receptor D<sub>1</sub>]] activity ''in vivo'' <ref>{{cite journal | vauthors = Fernandes-Cerqueira C, Sampaio-Maia B, Quelhas-Santos J, Moreira-Rodrigues M, Simões-Silva L, Blazquez-Medela AM, Martinez-Salgado C, Lopez-Novoa JM, Pestana M | title = Concerted action of ANP and dopamine D1-receptor to regulate sodium homeostasis in nephrotic syndrome | journal = BioMed Research International | volume = 2013 | pages = 397391 | date = 2013 | pmid = 23956981 | pmc = 3727124 | doi = 10.1155/2013/397391 }}</ref>
* Inhibits [[renin]] secretion, thereby inhibiting the [[renin–angiotensin–aldosterone system]].


There is no level of BNP that perfectly separates patients with and without heart failure:<ref name="pmid12124404">{{cite journal |author=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 |title=Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure |journal=N Engl J Med |volume=347 |issue=3 |pages=161-7 |year=2002 |doi=10.1056/NEJMoa020233|pmid=12124404}}</ref>
=== Adrenal ===


*BNP < 100 pg per milliliter:
* Reduces aldosterone secretion by the zona glomerulosa of the [[adrenal cortex]].
:* [[sensitivity (tests)|Sensitivity]] = 90%
:* [[specificity (tests)|Specificity]] = 76%


*BNP < 50 pg per milliliter:
=== Vascular ===
:* [[sensitivity (tests)|Sensitivity]] = 97%
:* [[specificity (tests)|Specificity]] = 62%


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.
Relaxes vascular smooth muscle in arterioles and venules by:
* Membrane Receptor-mediated elevation of vascular smooth muscle cGMP
* Inhibition of the effects of catecholamines


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 <ref name="pmid15337217">{{cite journal | author = 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 | title = Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus | journal = J. Am. Coll. Cardiol. | volume = 44 | issue = 5 | pages = 1047–52 | year = 2004 | month = September | pmid = 15337217 | doi = 10.1016/j.jacc.2004.05.071 | url =  }}</ref>. Also, BNP was found to have an important role in prognostication of heart surgery patients<ref name="pmid15145114">{{cite journal | author = Hutfless R, Kazanegra R, Madani M, Bhalla MA, Tulua-Tata A, Chen A, Clopton P, James C, Chiu A, Maisel AS | title = Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery | journal = J. Am. Coll. Cardiol. | volume = 43 | issue = 10 | pages = 1873–9 | year = 2004 | month = May | pmid = 15145114 | doi = 10.1016/j.jacc.2003.12.048 | url =  }}</ref> and in the emergency department.<ref name="pmid15364340">{{cite journal | author = Maisel A, Hollander JE, Guss D, McCullough P, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R | title = 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 | journal = J. Am. Coll. Cardiol. | volume = 44 | issue = 6 | pages = 1328–33 | year = 2004 | month = September | pmid = 15364340 | doi = 10.1016/j.jacc.2004.06.015 | url =  }}</ref> Bhalla et al. showed that combining BNP with other tools likeimpedence cardiography (ICG) can improve early diagnosis of heart failure and advance prevention strategies<ref name="pmid15752936">{{cite journal | author = Bhalla V, Isakson S, Bhalla MA, Lin JP, Clopton P, Gardetto N, Maisel AS | title = Diagnostic ability of B-type natriuretic peptide and impedance cardiography: testing to identify left ventricular dysfunction in hypertensive patients | journal = Am. J. Hypertens. | volume = 18 | issue = 2 Pt 2 | pages = 73S–81S | year = 2005 | month = February | pmid = 15752936 | doi = 10.1016/j.amjhyper.2004.11.044 | url =  }}</ref><ref name="pmid19181293">{{cite journal | author = Castellanos LR, Bhalla V, Isakson S, Daniels LB, Bhalla MA, Lin JP, Clopton P, Gardetto N, Hoshino M, Chiu A, Fitzgerald R, Maisel AS | title = B-type natriuretic peptide and impedance cardiography at the time of routine echocardiography predict subsequent heart failure events | journal = J. Card. Fail. | volume = 15 | issue = 1 | pages = 41–7 | year = 2009 | month = February | pmid = 19181293 | doi = 10.1016/j.cardfail.2008.09.003 | url =  }}</ref>.  Treatment of decompensated heart failure with [[diuretic]]s, vasodilators, [[ACE inhibitor]]s, [[ARB]]s, [[beta-blocker]]s and aldosterone antagonists can result in quick fall of BNP levels.
Promotes uterine spiral artery remodeling, which is important for preventing pregnancy-induced hypertension.<ref>{{cite journal | vauthors = Cui Y, Wang W, Dong N, Lou J, Srinivasan DK, Cheng W, Huang X, Liu M, Fang C, Peng J, Chen S, Wu S, Liu Z, Dong L, Zhou Y, Wu Q | title = Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy | journal = Nature | volume = 484 | issue = 7393 | pages = 246–50 | date = Apr 2012 | pmid = 22437503 | pmc = 3578422 | doi = 10.1038/nature10897 | bibcode = 2012Natur.484..246C }}</ref>


===Others===
=== Cardiac ===
Utility of BNP has also been explored in various settings like [[preeclampsia]], ICU and [[shock]] and [[end stage renal disease]] ([[ESRD]]).<ref name="pmid16098869">{{cite journal | author = Resnik JL, Hong C, Resnik R, Kazanegra R, Beede J, Bhalla V, Maisel A | title = Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women | journal = Am. J. Obstet. Gynecol. | volume = 193 | issue = 2 | pages = 450–4 | year = 2005 | month = August | pmid = 16098869 | doi = 10.1016/j.ajog.2004.12.006 | url =  }}</ref><ref name="pmid15286561">{{cite journal | author = Bhalla V, Bhalla MA, Maisel AS | title = Evolution of B-type natriuretic peptide in evaluation of intensive care unit shock | journal = Crit. Care Med. | volume = 32 | issue = 8 | pages = 1787–9 | year = 2004 | month = August | pmid = 15286561 | doi = 10.1097/01.CCM.0000135748.75590.54| url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=32&issue=8&spage=1787 }}</ref><ref name="pmid17239684">{{cite journal | author = Sheen V, Bhalla V, Tulua-Tata A, Bhalla MA, Weiss D, Chiu A, Abdeen O, Mullaney S, Maisel A | title = The use of B-type natriuretic peptide to assess volume status in patients with end-stage renal disease | journal = Am. Heart J. | volume = 153 | issue = 2 | pages = 244.e1–5 | year = 2007 | month = February | pmid = 17239684 | doi = 10.1016/j.ahj.2006.10.041 | url =  }}</ref><ref name="pmid16763507">{{cite journal |author=Rudiger A, Gasser S, Fischler M, Hornemann T, von Eckardstein A, Maggiorini M |title=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 |journal=[[Critical Care Medicine]] |volume=34 |issue=8 |pages=2140–4 |year=2006 |month=August |pmid=16763507 |doi=10.1097/01.CCM.0000229144.97624.90 |url=}}</ref>  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]] <ref name="pmid15120816">{{cite journal |author=Mehra MR, Uber PA, Park MH, ''et al.'' |title=Obesity and suppressed B-type natriuretic peptide levels in heart failure |journal=[[Journal of the American College of Cardiology]] |volume=43 |issue=9 |pages=1590–5 |year=2004 |month=May |pmid=15120816 |doi=10.1016/j.jacc.2003.10.066 |url=}}</ref>.  Unlike BNP, NT-pro BNP is solely reliant on the kidney for excretion. Other medical conditions that can cause elevation of BNP levels include:
* [[Hypertension]]
* [[Myocardial infarction]]
* [[Atrial fibrillation]]
* [[Cirrhosis]]
* [[Pulmonary hypertension]]
* [[Pneumonia]]
* [[Acute respiratory distress syndrome]] ([[ARDS]])
* [[pulmonary embolism]]
* [[Chronic obstructive pulmonary disease]] ([[COPD]])
* Severe [[valvular heart disease]]s


For reasons unknown female gender and elderly age are also associated with elevated BNP levels. <ref name="pmid12225726">{{cite journal |author=Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC |title=Plasma brain natriuretic peptide concentration: impact of age and gender |journal=[[Journal of the American College of Cardiology]] |volume=40 |issue=5 |pages=976–82 |year=2002 |month=September |pmid=12225726 |doi= |url=}}</ref><ref name="pmid12127613">{{cite journal |author=Wang TJ, Larson MG, Levy D, ''et al.'' |title=Impact of age and sex on plasma natriuretic peptide levels in healthy adults |journal=[[The American Journal of Cardiology]] |volume=90 |issue=3 |pages=254–8 |year=2002 |month=August |pmid=12127613 |doi= |url=}}</ref>  
* Inhibits maladaptive cardiac hypertrophy
* Mice lacking cardiac NPRA develop increased cardiac mass and severe fibrosis and die suddenly<ref>{{cite journal | vauthors = Kong X, Wang X, Hellermann G, Lockey RF, Mohapatra S | year = 2007 | title = Mice Deficient in Atrial Natriuretic Peptide Receptor A (NPRA) Exhibit Decreased Lung Inflammation: Implication of NPRA Signaling in Asthma Pathogenesis | journal = The Journal of Allergy and Clinical Immunology | volume = 119 | issue = 1 | pages = S127 | doi = 10.1016/j.jaci.2006.11.482}}</ref>
* Re-expression of NPRA rescues the phenotype.


BNP is also marketed as [[nesiritide]] for the treatment of acute decompensated congestive heart failure.<ref name="pmid">{{cite journal | author = Bibbins-Domingo K, Gupta R, Na B, Wu A H B, Schiller N B, Whooley M A | title = ''N''-Terminal Fragment of the Prohormone Brain-Type Natriuretic Peptide (NT-proBNP), Cardiovascular Events, and Mortality in Patients With Stable Coronary Heart Disease. | jornal = JAMA | volume = 297 | issue = 2 | pages = 169-176 | year = 2007 | pmid=17213400 }} ''[http://jama.ama-assn.org/cgi/content/abstract/297/2/169 JAMA Abstract].''</ref>
=== Adipose tissue ===


==References==
* Increases the release of [[free fatty acid]]s from adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
{{reflist|2}}
* Activates adipocyte plasma membrane type A guanylyl cyclase receptors [[Natriuretic peptide receptor A|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]]-I (cGK-I)
* Does not modulate [[Cyclic adenosine monophosphate|cAMP]] production or [[Protein kinase A|PKA]] activity


==Further Reading==
== Measurement ==
BNP and NT-proBNP are measured by [[immunoassay]].<ref name="pmid22910582">{{cite journal |vauthors=Clerico A, Zaninotto M, Prontera C, Giovannini S, Ndreu R, Franzini M, Zucchelli GC, Plebani M | title = State of the art of BNP and NT-proBNP immunoassays: the CardioOrmoCheck study | journal = Clin. Chim. Acta | volume = 414 | issue = | pages = 112–9 |date=December 2012 | pmid = 22910582 | doi = 10.1016/j.cca.2012.07.017 }}</ref>
 
===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 {{Dubious|date=April 2014}}.<ref name="pmid12124404">{{cite journal |vauthors=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 |title=Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure |journal=N Engl J Med |volume=347 |issue=3 |pages=161–7 |year=2002 |doi=10.1056/NEJMoa020233|pmid=12124404}}</ref>
*Either BNP or NT-proBNP can also be used for screening and prognosis of heart failure.<ref name="pmid14872150">{{cite journal |vauthors=Bhalla V, Willis S, Maisel AS | title = B-type natriuretic peptide: the level and the drug--partners in the diagnosis of heart failure | journal = Congest Heart Fail | doi = 10.1111/j.1527-5299.2004.03310.x | pmid=14872150 | volume=10 | issue=1 Suppl 1 | year=2004 | pages=3–27}}</ref>
*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).<ref name="pmid15389242">{{cite journal |vauthors=Atisha D, Bhalla MA, Morrison LK, Felicio L, Clopton P, Gardetto N, Kazanegra R, Chiu A, Maisel AS | title = A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction | journal = Am. Heart J. | volume = 148 | issue = 3 | pages = 518–23 |date=September 2004 | pmid = 15389242 | doi = 10.1016/j.ahj.2004.03.014 }}</ref>
 
A preoperative BNP can be predictive of a risk of an acute cardiac events during cardiac surgeries.  A [[cutoff (reference value)|cutoff]] of 100 pg/ml has a [[sensitivity and specificity|sensitivity]] of approximately 100%, a [[negative predictive value]] of approximately 100%, a [[sensitivity and specificity|specificity]] of 90%, and a [[positive predictive value]] of 78% according to data from the [[United Kingdom]].<ref name="Berry2005">{{cite journal|last1=Berry|first1=C|title=Predictive value of plasma brain natriuretic peptide for cardiac outcome after vascular surgery|journal=Heart|volume=92|issue=3|year=2005|pages=401–402|issn=1355-6037|doi=10.1136/hrt.2005.060988|pmc=1860808}}</ref>
 
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.<ref name="pmid16938661">{{cite journal |vauthors=Austin WJ, Bhalla V, Hernandez-Arce I, Isakson SR, Beede J, Clopton P, Maisel AS, Fitzgerald RL | title = Correlation and prognostic utility of B-type natriuretic peptide and its amino-terminal fragment in patients with chronic kidney disease | journal = Am. J. Clin. Pathol. | volume = 126 | issue = 4 | pages = 506–12 |date=October 2006 | pmid = 16938661 | doi = 10.1309/M7AAXA0J1THMNCDF }}</ref><ref name="pmid16644321">{{cite journal |vauthors=Daniels LB, Clopton P, Bhalla V, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA, Maisel AS | title = How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study | journal = Am. Heart J. | volume = 151 | issue = 5 | pages = 999–1005 |date=May 2006 | pmid = 16644321 | doi = 10.1016/j.ahj.2005.10.011 }}</ref>
 
Low BNP was found to be a predictor of survival to age 90 in men.<ref>{{cite journal |author1=Nilsson, G |author2=Hedberg P |author3=Ohrvik J |title=How to live until 90 – Factors predicting survival in 75-year-olds from the general population |journal=Healthy Aging Research |volume=3 |issue=5 |pages=1–10 |year=2014 |doi=10.12715/har.2014.3.5}}</ref>
 
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.<ref name="pmid16431187">{{cite journal |vauthors=Strunk A, Bhalla V, Clopton P, Nowak RM, McCord J, Hollander JE, Duc P, Storrow AB, Abraham WT, Wu AH, Steg G, Perez A, Kazanegra R, Herrmann HC, Aumont MC, McCullough PA, Maisel A | title = Impact of the history of congestive heart failure on the utility of B-type natriuretic peptide in the emergency diagnosis of heart failure: results from the Breathing Not Properly Multinational Study | journal = Am. J. Med. | volume = 119 | issue = 1 | pages = 69.e1–11 |date=January 2006 | pmid = 16431187 | doi = 10.1016/j.amjmed.2005.04.029 }}</ref><ref name="pmid16644322">{{cite journal |vauthors=Brenden CK, Hollander JE, Guss D, McCullough PA, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R, Maisel AS | title = Gray zone BNP levels in heart failure patients in the emergency department: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study | journal = Am. Heart J. | volume = 151 | issue = 5 | pages = 1006–11 |date=May 2006 | pmid = 16644322 | doi = 10.1016/j.ahj.2005.10.017 }}</ref>
 
BNP may be a reliable predictor of cardiovascular mortality in diabetics.<ref name="pmid15337217">{{cite journal |vauthors=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 | title = Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus | journal = J. Am. Coll. Cardiol. | volume = 44 | issue = 5 | pages = 1047–52 |date=September 2004 | pmid = 15337217 | doi = 10.1016/j.jacc.2004.05.071 }}</ref>
 
BNP was found to have an important role in prognostication of heart surgery patients<ref name="pmid15145114">{{cite journal |vauthors=Hutfless R, Kazanegra R, Madani M, Bhalla MA, Tulua-Tata A, Chen A, Clopton P, James C, Chiu A, Maisel AS | title = Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery | journal = J. Am. Coll. Cardiol. | volume = 43 | issue = 10 | pages = 1873–9 |date=May 2004 | pmid = 15145114 | doi = 10.1016/j.jacc.2003.12.048 }}</ref> and in the emergency department.<ref name="pmid15364340">{{cite journal |vauthors=Maisel A, Hollander JE, Guss D, McCullough P, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R | title = 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 | journal = J. Am. Coll. Cardiol. | volume = 44 | issue = 6 | pages = 1328–33 |date=September 2004 | pmid = 15364340 | doi = 10.1016/j.jacc.2004.06.015 }}</ref> Bhalla et al. showed that combining BNP with other tools like ICG can improve early diagnosis of heart failure and advance prevention strategies.<ref name="pmid15752936">{{cite journal |vauthors=Bhalla V, Isakson S, Bhalla MA, Lin JP, Clopton P, Gardetto N, Maisel AS | title = Diagnostic ability of B-type natriuretic peptide and impedance cardiography: testing to identify left ventricular dysfunction in hypertensive patients | journal = Am. J. Hypertens. | volume = 18 | issue = 2 Pt 2 | pages = 73S–81S |date=February 2005 | pmid = 15752936 | doi = 10.1016/j.amjhyper.2004.11.044 }}</ref><ref name="pmid19181293">{{cite journal |vauthors=Castellanos LR, Bhalla V, Isakson S, Daniels LB, Bhalla MA, Lin JP, Clopton P, Gardetto N, Hoshino M, Chiu A, Fitzgerald R, Maisel AS | title = B-type natriuretic peptide and impedance cardiography at the time of routine echocardiography predict subsequent heart failure events | journal = J. Card. Fail. | volume = 15 | issue = 1 | pages = 41–7 |date=February 2009 | pmid = 19181293 | doi = 10.1016/j.cardfail.2008.09.003 }}</ref> Utility of BNP has also been explored in various settings like preeclampsia, ICU and shock and ESRD.<ref name="pmid16098869">{{cite journal |vauthors=Resnik JL, Hong C, Resnik R, Kazanegra R, Beede J, Bhalla V, Maisel A | title = Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women | journal = Am. J. Obstet. Gynecol. | volume = 193 | issue = 2 | pages = 450–4 |date=August 2005 | pmid = 16098869 | doi = 10.1016/j.ajog.2004.12.006 }}</ref><ref name="pmid15286561">{{cite journal |vauthors=Bhalla V, Bhalla MA, Maisel AS | title = Evolution of B-type natriuretic peptide in evaluation of intensive care unit shock | journal = Crit. Care Med. | volume = 32 | issue = 8 | pages = 1787–9 |date=August 2004 | pmid = 15286561 | doi = 10.1097/01.CCM.0000135748.75590.54| url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=32&issue=8&spage=1787 }}</ref><ref name="pmid17239684">{{cite journal |vauthors=Sheen V, Bhalla V, Tulua-Tata A, Bhalla MA, Weiss D, Chiu A, Abdeen O, Mullaney S, Maisel A | title = The use of B-type natriuretic peptide to assess volume status in patients with end-stage renal disease | journal = Am. Heart J. | volume = 153 | issue = 2 | pages = 244.e1–5 |date=February 2007 | pmid = 17239684 | doi = 10.1016/j.ahj.2006.10.041 }}</ref>
 
The effect or race and gender on value of BNP and its utility in that context has been studied extensively.<ref name="pmid15199359">{{cite journal |vauthors=Maisel AS, Clopton P, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Steg G, Westheim A, Knudsen CW, Perez A, Kazanegra R, Bhalla V, Herrmann HC, Aumont MC, McCullough PA | title = Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study | journal = Am. Heart J. | volume = 147 | issue = 6 | pages = 1078–84 |date=June 2004 | pmid = 15199359 | doi = 10.1016/j.ahj.2004.01.013 }}</ref><ref name="pmid16679261">{{cite journal |vauthors=Daniels LB, Bhalla V, Clopton P, Hollander JE, Guss D, McCullough PA, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Jesse R, Maisel A | title = B-type natriuretic peptide (BNP) levels and ethnic disparities in perceived severity of heart failure: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study of BNP levels and emergency department decision making in patients presenting with shortness of breath | journal = J. Card. Fail. | volume = 12 | issue = 4 | pages = 281–5 |date=May 2006 | pmid = 16679261 | doi = 10.1016/j.cardfail.2006.01.008 }}</ref>
 
{| class="wikitable"
|+ NT-proBNP levels (in pg/mL) by NYHA functional class <ref name="University of Iowa Department of Pathology Laboratory Services Handbook">{{cite web|url=http://www.medicine.uiowa.edu/path_handbook/handbook/test2621.html|title=N-terminal pro-BNP|deadurl=yes|archiveurl=https://web.archive.org/web/20081011225930/http://www.medicine.uiowa.edu/Path_Handbook/handbook/test2621.html|archivedate=2008-10-11|df=}}</ref>
! !! 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
|}
 
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.<ref name="pmid21135296">{{cite journal |vauthors=Lam LL, Cameron PA, Schneider HG, Abramson MJ, Müller C, Krum H | title = Meta-analysis: effect of B-type natriuretic peptide testing on clinical outcomes in patients with acute dyspnea in the emergency setting | journal = Ann. Intern. Med. | volume = 153 | issue = 11 | pages = 728–35 |date=December 2010 | pmid = 21135296 | doi = 10.7326/0003-4819-153-11-201012070-00006 }}</ref> The BNP test is also used for the risk stratification of patients with acute coronary syndromes.<ref name="pmid17213400">{{cite journal |vauthors=Bibbins-Domingo K, Gupta R, Na B, Wu AH, Schiller NB, Whooley MA | title = N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease | journal = JAMA | volume = 297 | issue = 2 | pages = 169–76 |date=January 2007 | pmid = 17213400 | doi = 10.1001/jama.297.2.169 | url = | pmc = 2848442 }}</ref><ref name="pmid16169326">{{cite journal |vauthors=Fitzgerald RL, Cremo R, Gardetto N, Chiu A, Clopton P, Bhalla V, Maisel AS | title = Effect of nesiritide in combination with standard therapy on serum concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure | journal = Am. Heart J. | volume = 150 | issue = 3 | pages = 471–7 |date=September 2005 | pmid = 16169326 | doi = 10.1016/j.ahj.2004.11.021 }}</ref>
 
When interpreting an elevated BNP level, it is useful to remember that values may be elevated due to factors other than heart failure. Lower levels are often seen in obese patients.<ref name="Wang">{{cite journal |vauthors=Wang TJ, Larson MG, Levy D | title = Impact of obesity on plasma natriuretic peptide levels | journal = Circulation | volume = 109 | pages = 594–600 | year = 2004 | pmid = 14769680 | doi = 10.1161/01.CIR.0000112582.16683.EA | issue = 5 |display-authors=etal}}</ref> 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<ref name="pmid21732835">{{cite journal |vauthors=O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, Heizer GM, Komajda M, Massie BM, McMurray JJ | title = Effect of nesiritide in patients with acute decompensated heart failure | journal = N. Engl. J. Med. | volume = 365 | issue = 1 | pages = 32–43 |date=July 2011 | pmid = 21732835 | doi = 10.1056/NEJMoa1100171 |display-authors=etal}}</ref> 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 II receptor blocker|angiotensin receptor blockers]] has been shown to be advantageous to [[ACE inhibitor|ACE inhibitors]], the current first-line therapy, in multiple settings.<ref>{{Cite journal|last=McMurray|first=John J.V.|last2=Packer|first2=Milton|last3=Desai|first3=Akshay S.|last4=Gong|first4=Jianjian|last5=Lefkowitz|first5=Martin P.|last6=Rizkala|first6=Adel R.|last7=Rouleau|first7=Jean L.|last8=Shi|first8=Victor C.|last9=Solomon|first9=Scott D.|date=2014-09-11|title=Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure|url=https://doi.org/10.1056/NEJMoa1409077|journal=New England Journal of Medicine|volume=371|issue=11|pages=993–1004|doi=10.1056/NEJMoa1409077|issn=0028-4793|pmid=25176015}}</ref><ref>{{Cite journal|last=Velazquez|first=Eric J.|last2=Morrow|first2=David A.|last3=DeVore|first3=Adam D.|last4=Duffy|first4=Carol I.|last5=Ambrosy|first5=Andrew P.|last6=McCague|first6=Kevin|last7=Rocha|first7=Ricardo|last8=Braunwald|first8=Eugene|date=2018-11-11|title=Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure|url=https://doi.org/10.1056/NEJMoa1812851|journal=New England Journal of Medicine|volume=0|issue=0|pages=null|doi=10.1056/NEJMoa1812851|issn=0028-4793|pmid=30415601}}</ref>
 
==Synonyms==
Other terms for BNP include ''B-type natriuretic peptide''', '''ventricular natriuretic peptide''' and '''natriuretic peptide B''')
 
== See also ==
* [[C-type natriuretic peptide]]
 
== References ==
{{reflist|30em}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal  | author=Cosson S |title=Usefulness of B-type natriuretic peptide (BNP) as a screen for left ventricular abnormalities in diabetes mellitus |journal=Diabetes Metab. |volume=30 |issue= 4 |pages= 381–6 |year= 2004 |pmid= 15525883 |doi=10.1016/S1262-3636(07)70132-5 }}
| citations =
*{{cite journal  |vauthors=Cauliez B, Berthe MC, Lavoinne A |title=[Brain natriuretic peptide: physiological, biological and clinical aspects] |journal=Ann. Biol. Clin. |location = Paris |volume=63 |issue= 1 |pages= 15–25 |year= 2005 |pmid= 15689309 |doi= }}
*{{cite journal  | author=Cosson S |title=Usefulness of B-type natriuretic peptide (BNP) as a screen for left ventricular abnormalities in diabetes mellitus. |journal=Diabetes Metab. |volume=30 |issue= 4 |pages= 381-6 |year= 2004 |pmid= 15525883 |doi= }}
*{{cite journal  |vauthors=Buchner S, Riegger G, Luchner A |title=[Clinical utility of the cardiac markers BNP and NT-proBNP] |journal=Acta Med. Austriaca |volume=31 |issue= 4 |pages= 144–51 |year= 2005 |pmid= 15732251 |doi= }}
*{{cite journal  | author=Cauliez B, Berthe MC, Lavoinne A |title=[Brain natriuretic peptide: physiological, biological and clinical aspects] |journal=Ann. Biol. Clin. (Paris) |volume=63 |issue= 1 |pages= 15-25 |year= 2005 |pmid= 15689309 |doi= }}
*{{cite journal  | author=LaPointe MC |title=Molecular regulation of the brain natriuretic peptide gene |journal=Peptides |volume=26 |issue= 6 |pages= 944–56 |year= 2005 |pmid= 15911064 |doi= 10.1016/j.peptides.2004.08.028 }}
*{{cite journal  | author=Buchner S, Riegger G, Luchner A |title=[Clinical utility of the cardiac markers BNP and NT-proBNP] |journal=Acta Med. Austriaca |volume=31 |issue= 4 |pages= 144-51 |year= 2005 |pmid= 15732251 |doi= }}
*{{cite journal  |vauthors=Hoffmann U, Borggrefe M, Brueckmann M |title=New horizons: NT-proBNP for risk stratification of patients with shock in the intensive care unit |journal=Critical care (London, England) |volume=10 |issue= 2 |pages= 134 |year= 2006 |pmid= 16594987 |doi= 10.1186/cc4883 | pmc=1550883 }}
*{{cite journal  | author=LaPointe MC |title=Molecular regulation of the brain natriuretic peptide gene. |journal=Peptides |volume=26 |issue= 6 |pages= 944-56 |year= 2005 |pmid= 15911064 |doi= 10.1016/j.peptides.2004.08.028 }}
*{{cite journal  |vauthors=Suga S, Nakao K, Hosoda K |title=Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide |journal=Endocrinology |volume=130 |issue= 1 |pages= 229–39 |year= 1992 |pmid= 1309330 |doi=10.1210/en.130.1.229 |display-authors=etal}}
*{{cite journal  | author=Hoffmann U, Borggrefe M, Brueckmann M |title=New horizons: NT-proBNP for risk stratification of patients with shock in the intensive care unit. |journal=Critical care (London, England) |volume=10 |issue= 2 |pages= 134 |year= 2006 |pmid= 16594987 |doi= 10.1186/cc4883 }}
*{{cite journal  |vauthors=Kambayashi Y, Nakao K, Mukoyama M |title=Isolation and sequence determination of human brain natriuretic peptide in human atrium |journal=FEBS Lett. |volume=259 |issue= 2 |pages= 341–5 |year= 1990 |pmid= 2136732 |doi=10.1016/0014-5793(90)80043-I |display-authors=etal}}
*{{cite journal  | author=Suga S, Nakao K, Hosoda K, ''et al.'' |title=Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide. |journal=Endocrinology |volume=130 |issue= 1 |pages= 229-39 |year= 1992 |pmid= 1309330 |doi= }}
*{{cite journal  |vauthors=Hino J, Tateyama H, Minamino N |title=Isolation and identification of human brain natriuretic peptides in cardiac atrium |journal=Biochem. Biophys. Res. Commun. |volume=167 |issue= 2 |pages= 693–700 |year= 1990 |pmid= 2138890 |doi=10.1016/0006-291X(90)92081-A |display-authors=etal}}
*{{cite journal  | author=Kambayashi Y, Nakao K, Mukoyama M, ''et al.'' |title=Isolation and sequence determination of human brain natriuretic peptide in human atrium. |journal=FEBS Lett. |volume=259 |issue= 2 |pages= 341-5 |year= 1990 |pmid= 2136732 |doi= }}
*{{cite journal  |vauthors=Sudoh T, Maekawa K, Kojima M |title=Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide |journal=Biochem. Biophys. Res. Commun. |volume=159 |issue= 3 |pages= 1427–34 |year= 1989 |pmid= 2522777 |doi=10.1016/0006-291X(89)92269-9 |display-authors=etal}}
*{{cite journal  | author=Hino J, Tateyama H, Minamino N, ''et al.'' |title=Isolation and identification of human brain natriuretic peptides in cardiac atrium. |journal=Biochem. Biophys. Res. Commun. |volume=167 |issue= 2 |pages= 693-700 |year= 1990 |pmid= 2138890 |doi= }}
*{{cite journal  |vauthors=Seilhamer JJ, Arfsten A, Miller JA |title=Human and canine gene homologs of porcine brain natriuretic peptide |journal=Biochem. Biophys. Res. Commun. |volume=165 |issue= 2 |pages= 650–8 |year= 1990 |pmid= 2597152 |doi=10.1016/S0006-291X(89)80015-4 |display-authors=etal}}
*{{cite journal  | author=Sudoh T, Maekawa K, Kojima M, ''et al.'' |title=Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide. |journal=Biochem. Biophys. Res. Commun. |volume=159 |issue= 3 |pages= 1427-34 |year= 1989 |pmid= 2522777 |doi= }}
*{{cite journal  |vauthors=Arden KC, Viars CS, Weiss S |title=Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome 1p36 |journal=Genomics |volume=26 |issue= 2 |pages= 385–9 |year= 1995 |pmid= 7601467 |doi=10.1016/0888-7543(95)80225-B |display-authors=etal}}
*{{cite journal  | author=Seilhamer JJ, Arfsten A, Miller JA, ''et al.'' |title=Human and canine gene homologs of porcine brain natriuretic peptide. |journal=Biochem. Biophys. Res. Commun. |volume=165 |issue= 2 |pages= 650-8 |year= 1990 |pmid= 2597152 |doi= }}
*{{cite journal  |vauthors=Weir ML, Pang SC, Flynn TG |title=Characterization of binding sites in rat for A, B and C-type natriuretic peptides |journal=Regul. Pept. |volume=47 |issue= 3 |pages= 291–305 |year= 1993 |pmid= 7901875 |doi=10.1016/0167-0115(93)90396-P }}
*{{cite journal  | author=Arden KC, Viars CS, Weiss S, ''et al.'' |title=Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome 1p36. |journal=Genomics |volume=26 |issue= 2 |pages= 385-9 |year= 1995 |pmid= 7601467 |doi= }}
*{{cite journal  |vauthors=Totsune K, Takahashi K, Satoh F |title=Urinary immunoreactive brain natriuretic peptide in patients with renal disease |journal=Regul. Pept. |volume=63 |issue= 2–3 |pages= 141–7 |year= 1996 |pmid= 8837222 |doi=10.1016/0167-0115(96)00035-3 |display-authors=etal}}
*{{cite journal  | author=Weir ML, Pang SC, Flynn TG |title=Characterization of binding sites in rat for A, B and C-type natriuretic peptides. |journal=Regul. Pept. |volume=47 |issue= 3 |pages= 291-305 |year= 1993 |pmid= 7901875 |doi= }}
*{{cite journal  |vauthors=Totsune K, Takahashi K, Murakami O |title=Immunoreactive brain natriuretic peptide in human adrenal glands and adrenal tumors |journal=Eur. J. Endocrinol. |volume=135 |issue= 3 |pages= 352–6 |year= 1996 |pmid= 8890728 |doi=10.1530/eje.0.1350352 |display-authors=etal}}
*{{cite journal  | author=Totsune K, Takahashi K, Satoh F, ''et al.'' |title=Urinary immunoreactive brain natriuretic peptide in patients with renal disease. |journal=Regul. Pept. |volume=63 |issue= 2-3 |pages= 141-7 |year= 1996 |pmid= 8837222 |doi= }}
*{{cite journal  |vauthors=Matsuo K, Nishikimi T, Yutani C |title=Diagnostic value of plasma levels of brain natriuretic peptide in arrhythmogenic right ventricular dysplasia |journal=Circulation |volume=98 |issue= 22 |pages= 2433–40 |year= 1999 |pmid= 9832489 |doi=10.1161/01.CIR.98.22.2433 |display-authors=etal}}
*{{cite journal  | author=Totsune K, Takahashi K, Murakami O, ''et al.'' |title=Immunoreactive brain natriuretic peptide in human adrenal glands and adrenal tumors. |journal=Eur. J. Endocrinol. |volume=135 |issue= 3 |pages= 352-6 |year= 1996 |pmid= 8890728 |doi= }}
*{{cite journal  |vauthors=Wiese S, Breyer T, Dragu A |title=Gene expression of brain natriuretic peptide in isolated atrial and ventricular human myocardium: influence of angiotensin II and diastolic fiber length |journal=Circulation |volume=102 |issue= 25 |pages= 3074–9 |year= 2001 |pmid= 11120697 |doi=10.1161/01.CIR.102.25.3074 |display-authors=etal}}
*{{cite journal  | author=Matsuo K, Nishikimi T, Yutani C, ''et al.'' |title=Diagnostic value of plasma levels of brain natriuretic peptide in arrhythmogenic right ventricular dysplasia. |journal=Circulation |volume=98 |issue= 22 |pages= 2433-40 |year= 1999 |pmid= 9832489 |doi= }}
*{{cite journal  |vauthors=Shimizu H, Masuta K, Aono K |title=Molecular forms of human brain natriuretic peptide in plasma |journal=Clin. Chim. Acta |volume=316 |issue= 1–2 |pages= 129–35 |year= 2002 |pmid= 11750283 |doi=10.1016/S0009-8981(01)00745-8 |display-authors=etal}}
*{{cite journal  | author=Wiese S, Breyer T, Dragu A, ''et al.'' |title=Gene expression of brain natriuretic peptide in isolated atrial and ventricular human myocardium: influence of angiotensin II and diastolic fiber length. |journal=Circulation |volume=102 |issue= 25 |pages= 3074-9 |year= 2001 |pmid= 11120697 |doi= }}
*{{cite journal  |vauthors=Ogawa K, Oida A, Sugimura H |title=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 |journal=Circ. J. |volume=66 |issue= 2 |pages= 122–6 |year= 2002 |pmid= 11999635 |doi=10.1253/circj.66.122 |display-authors=etal}}
*{{cite journal  | author=Shimizu H, Masuta K, Aono K, ''et al.'' |title=Molecular forms of human brain natriuretic peptide in plasma. |journal=Clin. Chim. Acta |volume=316 |issue= 1-2 |pages= 129-35 |year= 2002 |pmid= 11750283 |doi= }}
*{{cite journal  |vauthors=Asakawa H, Fukui T, Tokunaga K, Kawakami F |title=Plasma brain natriuretic peptide levels in normotensive Type 2 diabetic patients without cardiac disease and macroalbuminuria |journal=J. Diabetes Complicat. |volume=16 |issue= 3 |pages= 209–13 |year= 2002 |pmid= 12015190 |doi=10.1016/S1056-8727(01)00173-8 }}
*{{cite journal  | author=Ogawa K, Oida A, Sugimura H, ''et al.'' |title=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. |journal=Circ. J. |volume=66 |issue= 2 |pages= 122-6 |year= 2002 |pmid= 11999635 |doi= }}
*{{cite journal  |vauthors=Bordenave L, Georges A, Bareille R |title=Human bone marrow endothelial cells: a new identified source of B-type natriuretic peptide |journal=Peptides |volume=23 |issue= 5 |pages= 935–40 |year= 2003 |pmid= 12084525 |doi=10.1016/S0196-9781(02)00004-9 |display-authors=etal}}
*{{cite journal  | author=Asakawa H, Fukui T, Tokunaga K, Kawakami F |title=Plasma brain natriuretic peptide levels in normotensive Type 2 diabetic patients without cardiac disease and macroalbuminuria. |journal=J. Diabetes Complicat. |volume=16 |issue= 3 |pages= 209-13 |year= 2002 |pmid= 12015190 |doi= }}
*{{cite journal  | author=Bordenave L, Georges A, Bareille R, ''et al.'' |title=Human bone marrow endothelial cells: a new identified source of B-type natriuretic peptide. |journal=Peptides |volume=23 |issue= 5 |pages= 935-40 |year= 2003 |pmid= 12084525 |doi= }}
}}
{{refend}}
{{refend}}


==External Links==
==External links==
* {{MeshName|Brain+Natriuretic+Peptide}}
* {{MeshName|Brain+Natriuretic+Peptide}}
<br>
* BNP and NT-proBNP at [http://labtestsonline.org/understanding/analytes/bnp/tab/test Lab Tests Online]
* {{UCSC gene info|NPPB}}


{{Hormones}}
{{Nerve tissue protein}}


[[Category:Cardiology]]
[[Category:Cardiology]]
[[de:Brain Natriuretic Peptide]]
[[fr:BNP (biologie)]]
[[ja:脳性ナトリウム利尿ペプチド]]
[[pl:Mózgowy peptyd natriuretyczny]]
{{WH}}
{{WS}}

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Brain natriuretic peptide (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. BNP is named as such because it was originally identified in extracts of pig brain.

The 32-amino acid polypeptide BNP is secreted attached to a 76–amino acid N-terminal fragment in the prohormone called NT-proBNP (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, 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 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.[1]

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; 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.[2] Cleavage at other sites produces shorter BNP peptides with unknown biological activity.[3] Processing of proBNP may be regulated by O-glycosylation of residues near the cleavage sites.[4]

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 binding causes a reduction in renal sodium reabsorption, 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

Adrenal

  • Reduces aldosterone secretion by the zona glomerulosa of the adrenal cortex.

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.[8]

Cardiac

  • Inhibits maladaptive cardiac hypertrophy
  • Mice lacking cardiac NPRA develop increased cardiac mass and severe fibrosis and die suddenly[9]
  • 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-I (cGK-I)
  • Does not modulate cAMP production or PKA activity

Measurement

BNP and NT-proBNP are measured by immunoassay.[10]

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[dubious ].[11]
  • Either BNP or NT-proBNP can also be used for screening and prognosis of heart failure.[12]
  • 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).[13]

A preoperative BNP can be predictive of a risk of an acute cardiac events during cardiac surgeries. A cutoff of 100 pg/ml has a sensitivity of approximately 100%, a negative predictive value of approximately 100%, a specificity of 90%, and a positive predictive value of 78% according to data from the United Kingdom.[14]

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.[15][16]

Low BNP was found to be a predictor of survival to age 90 in men.[17]

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.[18][19]

BNP may be a reliable predictor of cardiovascular mortality in diabetics.[20]

BNP was found to have an important role in prognostication of heart surgery patients[21] and in the emergency department.[22] Bhalla et al. showed that combining BNP with other tools like ICG can improve early diagnosis of heart failure and advance prevention strategies.[23][24] Utility of BNP has also been explored in various settings like preeclampsia, ICU and shock and ESRD.[25][26][27]

The effect or race and gender on value of BNP and its utility in that context has been studied extensively.[28][29]

NT-proBNP levels (in pg/mL) by NYHA functional class [30]
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

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.[31] The BNP test is also used for the risk stratification of patients with acute coronary syndromes.[32][33]

When interpreting an elevated BNP level, it is useful to remember that values may be elevated due to factors other than heart failure. Lower levels are often seen in obese patients.[34] 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[35] 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 inhibitors, the current first-line therapy, in multiple settings.[36][37]

Synonyms

Other terms for BNP include B-type natriuretic peptide, ventricular natriuretic peptide and natriuretic peptide B')

See also

References

  1. "CV Pharmacology - Natriuretic Peptides". cvpharmacology.com. Archived from the original on 21 October 2017. Retrieved 29 April 2018.
  2. Schellenberger U, O'Rear J, Guzzetta A, Jue RA, Protter AA, Pollitt NS (July 2006). "The precursor to B-type natriuretic peptide is an O-linked glycoprotein". Arch. Biochem. Biophys. 451 (2): 160–6. doi:10.1016/j.abb.2006.03.028. PMID 16750161.
  3. Niederkofler EE, Kiernan UA, O'Rear J, Menon S, Saghir S, Protter AA, Nelson RW, Schellenberger U (November 2008). "Detection of endogenous B-type natriuretic peptide at very low concentrations in patients with heart failure". Circ Heart Fail. 1 (4): 258–64. doi:10.1161/CIRCHEARTFAILURE.108.790774. PMID 19808300.
  4. Semenov AG, Postnikov AB, Tamm NN, Seferian KR, Karpova NS, Bloshchitsyna MN, Koshkina EV, Krasnoselsky MI, Serebryanaya DV, Katrukha AG (March 2009). "Processing of pro-brain natriuretic peptide is suppressed by O-glycosylation in the region close to the cleavage site". Clin. Chem. 55 (3): 489–98. doi:10.1373/clinchem.2008.113373. PMID 19168558.
  5. Kiberd BA, Larson TS, Robertson CR, Jamison RL (Jun 1987). "Effect of atrial natriuretic peptide on vasa recta blood flow in the rat". The American Journal of Physiology. 252 (6 Pt 2): F1112–7. PMID 2954471. Archived from the original on 2009-01-08. Retrieved 2017-09-09.
  6. Reeves WB, Andreoli TE (2008). "Chapter 31 – Sodium Chloride Transport in the Loop of Henle, Distal Convoluted Tubule, and Collecting Duct". In Giebisch GH, Alpern RA, Herbert SC, Seldin DW. Seldin and Giebisch's the kidney: physiology and pathophysiology. Amsterdam: Elsevier/Academic Press. doi:10.1016/B978-012088488-9.50034-6. ISBN 0-12-088488-7.
  7. Fernandes-Cerqueira C, Sampaio-Maia B, Quelhas-Santos J, Moreira-Rodrigues M, Simões-Silva L, Blazquez-Medela AM, Martinez-Salgado C, Lopez-Novoa JM, Pestana M (2013). "Concerted action of ANP and dopamine D1-receptor to regulate sodium homeostasis in nephrotic syndrome". BioMed Research International. 2013: 397391. doi:10.1155/2013/397391. PMC 3727124. PMID 23956981.
  8. Cui Y, Wang W, Dong N, Lou J, Srinivasan DK, Cheng W, Huang X, Liu M, Fang C, Peng J, Chen S, Wu S, Liu Z, Dong L, Zhou Y, Wu Q (Apr 2012). "Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy". Nature. 484 (7393): 246–50. Bibcode:2012Natur.484..246C. doi:10.1038/nature10897. PMC 3578422. PMID 22437503.
  9. Kong X, Wang X, Hellermann G, Lockey RF, Mohapatra S (2007). "Mice Deficient in Atrial Natriuretic Peptide Receptor A (NPRA) Exhibit Decreased Lung Inflammation: Implication of NPRA Signaling in Asthma Pathogenesis". The Journal of Allergy and Clinical Immunology. 119 (1): S127. doi:10.1016/j.jaci.2006.11.482.
  10. Clerico A, Zaninotto M, Prontera C, Giovannini S, Ndreu R, Franzini M, Zucchelli GC, Plebani M (December 2012). "State of the art of BNP and NT-proBNP immunoassays: the CardioOrmoCheck study". Clin. Chim. Acta. 414: 112–9. doi:10.1016/j.cca.2012.07.017. PMID 22910582.
  11. 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.
  12. Bhalla V, Willis S, Maisel AS (2004). "B-type natriuretic peptide: the level and the drug--partners in the diagnosis of heart failure". Congest Heart Fail. 10 (1 Suppl 1): 3–27. doi:10.1111/j.1527-5299.2004.03310.x. PMID 14872150.
  13. Atisha D, Bhalla MA, Morrison LK, Felicio L, Clopton P, Gardetto N, Kazanegra R, Chiu A, Maisel AS (September 2004). "A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction". Am. Heart J. 148 (3): 518–23. doi:10.1016/j.ahj.2004.03.014. PMID 15389242.
  14. Berry, C (2005). "Predictive value of plasma brain natriuretic peptide for cardiac outcome after vascular surgery". Heart. 92 (3): 401–402. doi:10.1136/hrt.2005.060988. ISSN 1355-6037. PMC 1860808.
  15. Austin WJ, Bhalla V, Hernandez-Arce I, Isakson SR, Beede J, Clopton P, Maisel AS, Fitzgerald RL (October 2006). "Correlation and prognostic utility of B-type natriuretic peptide and its amino-terminal fragment in patients with chronic kidney disease". Am. J. Clin. Pathol. 126 (4): 506–12. doi:10.1309/M7AAXA0J1THMNCDF. PMID 16938661.
  16. Daniels LB, Clopton P, Bhalla V, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA, Maisel AS (May 2006). "How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study". Am. Heart J. 151 (5): 999–1005. doi:10.1016/j.ahj.2005.10.011. PMID 16644321.
  17. Nilsson, G; Hedberg P; Ohrvik J (2014). "How to live until 90 – Factors predicting survival in 75-year-olds from the general population". Healthy Aging Research. 3 (5): 1–10. doi:10.12715/har.2014.3.5.
  18. Strunk A, Bhalla V, Clopton P, Nowak RM, McCord J, Hollander JE, Duc P, Storrow AB, Abraham WT, Wu AH, Steg G, Perez A, Kazanegra R, Herrmann HC, Aumont MC, McCullough PA, Maisel A (January 2006). "Impact of the history of congestive heart failure on the utility of B-type natriuretic peptide in the emergency diagnosis of heart failure: results from the Breathing Not Properly Multinational Study". Am. J. Med. 119 (1): 69.e1–11. doi:10.1016/j.amjmed.2005.04.029. PMID 16431187.
  19. Brenden CK, Hollander JE, Guss D, McCullough PA, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R, Maisel AS (May 2006). "Gray zone BNP levels in heart failure patients in the emergency department: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study". Am. Heart J. 151 (5): 1006–11. doi:10.1016/j.ahj.2005.10.017. PMID 16644322.
  20. 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 (September 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.
  21. Hutfless R, Kazanegra R, Madani M, Bhalla MA, Tulua-Tata A, Chen A, Clopton P, James C, Chiu A, Maisel AS (May 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.
  22. Maisel A, Hollander JE, Guss D, McCullough P, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R (September 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.
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  24. Castellanos LR, Bhalla V, Isakson S, Daniels LB, Bhalla MA, Lin JP, Clopton P, Gardetto N, Hoshino M, Chiu A, Fitzgerald R, Maisel AS (February 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.
  25. Resnik JL, Hong C, Resnik R, Kazanegra R, Beede J, Bhalla V, Maisel A (August 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.
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  36. McMurray, John J.V.; Packer, Milton; Desai, Akshay S.; Gong, Jianjian; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean L.; Shi, Victor C.; Solomon, Scott D. (2014-09-11). "Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure". New England Journal of Medicine. 371 (11): 993–1004. doi:10.1056/NEJMoa1409077. ISSN 0028-4793. PMID 25176015.
  37. Velazquez, Eric J.; Morrow, David A.; DeVore, Adam D.; Duffy, Carol I.; Ambrosy, Andrew P.; McCague, Kevin; Rocha, Ricardo; Braunwald, Eugene (2018-11-11). "Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure". New England Journal of Medicine. 0 (0): null. doi:10.1056/NEJMoa1812851. ISSN 0028-4793. PMID 30415601.

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.
  • 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.
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  • 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. PMID 16594987.
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