European Journal of Heart Failure

European Journal of Heart Failure 2004 6(3):261-268; doi:10.1016/j.ejheart.2004.01.004

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Disclaimer Google Scholar Articles by Vanderheyden, M. Articles by Goethals, M. Search for Related Content PubMed PubMed Citation Articles by Vanderheyden, M. Articles by Goethals, M. Social Bookmarking          What's this?

© 2004 European Society of Cardiology

Brain and other natriuretic peptides: molecular aspects

Marc Vanderheyden^*, Jozef Bartunek and Marc Goethals

Cardiovascular Center, Onze Lieve Vrouwziekenhuis Moorselbaan 164, 9400 Aalst, Belgium

^* Corresponding author. Tel.: +32-53-724433; Fax: +32-53-724185 E-mail address: marc.vanderheyden{at}olvz-aalst.be

	Abstract

Top Abstract 1. Introduction 2. The natriuretic peptide... 3. Natriuretic peptide receptors 4. Clearance of natriuretic... 5. Regulation and induction... 6. Actions of the... 7. Conclusion References

 
Natriuretic peptides have emerged as important candidates for development of diagnostic tools and therapeutic agents in cardiovascular disease. The family contains of three major peptides—ANP, BNP, CNP—that participate in cardiovascular and cardiorenal homeostasis. Each of these natriuretic peptides binds differentially to specific receptors that signal through different mechanisms. They are cleared enzymatically by neutral endopeptidase as well as by receptor-mediated endocytosis. Because of its fast induction and specific expression in overt heart failure, BNP seems the most promising natriuretic peptide. It is predominantly synthesized in the cardiac ventricles, released as pre-proBNP and then enzymatically cleaved to BNP and the N-terminal portion of BNP(NT-proBNP). Blood measurements of BNP and NT-proBNP have been shown to identify patients with LV dysfunction. This review focuses on the physiology of natriuretic peptides as a group and brain natriuretic peptide in more detail, its structure and regulation as well as its effects at the cellular level.

Key Words: Natriuretic peptides • Heart failure

Received December 23, 2003; Accepted January 13, 2004

	1. Introduction

Top Abstract 1. Introduction 2. The natriuretic peptide... 3. Natriuretic peptide receptors 4. Clearance of natriuretic... 5. Regulation and induction... 6. Actions of the... 7. Conclusion References

 
Though it is well known that neurohormones are activated and released into the circulation in patients with heart failure, the therapeutic importance of this observation has only emerged in the past 10–15 years. To counter-balance the effects of vasoconstrictor-mitogenic-sodium-retaining neurohormones, released by the sympathetic nervous system and the RAAS, and to maintain circulatory homeostasis the body produces a family of vasodilator antiproliferative natriuretic peptides that have an important role in heart failure both as counter-regulatory hormones and as potential exogenous therapy.

In 1981 de Bold and colleagues observed that extracts of atrial tissue infused into rats caused a copious diuresis [1]. Subsequent isolation and purification quickly revealed that a new peptide called atrial natriuretic peptide was the mediator of this diuretic response [1]. Ten years following the description of atrial natriuretic peptide, a second compound of the family of natriuretic peptides was described. This was called brain natriuretic peptide because of it first isolation from porcine brain [2]. Over the past decade, it has been demonstrated that this peptide has great pathophysiological importance in diagnosing heart failure [3,4] as well as in risk stratification and guiding heart failure therapy [5]. This review focuses on natriuretic peptides as a group and brain natriuretic peptide in more detail, its structure and regulation as well as its effects at the cellular level.

	2. The natriuretic peptide family

Top Abstract 1. Introduction 2. The natriuretic peptide... 3. Natriuretic peptide receptors 4. Clearance of natriuretic... 5. Regulation and induction... 6. Actions of the... 7. Conclusion References

 
Four distinct natriuretic peptides have been described (Table 1). They all have a characteristic 17 amino-acid residue ring structure formed by an intramolecular disulfide bridge between two cysteine residues [6]. The amino- and carboxyl terminal tails varies between the different peptides leading to polypeptides of 28 amino acids (ANP), 32 amino acids (BNP), 53 amino acids (CNP) and 38 amino acids for D-type [7]. They all also exist as a pro-hormone with a relatively high molecular weight that is cleaved before release into the circulation [8].

View this table: [in this window] [in a new window]   Table 1 Characteristics of the natriuretic peptides

 
The ANP and BNP precursor peptide genes reside in tandem on the distal short arm of chromosome 1 [9]whereas the CNP precursor peptide gene is localized on chromosome 2 [9]. The gene encoding DNP has not been cloned [10].

2.1. Atrial natriuretic peptide
The messenger RNA transcript for atrial natriuretic peptide is approximately 1 kb in size and encodes a precursor protein (pro-atrial natriuretic peptide) of 126 amino acids. Human pro-atrial natriuretic peptide is proteolytically cleaved to a 98-amino-acid amino-terminal fragment and a 28-amino-acid carboxy-terminal fragment that represents biologically active ANP [11]. Both fragments as well as other fragments of the amino-terminal molecule circulate in plasma. Several data suggest that these pro-ANP fragments may be as or even more important than ANP as a natriuretic hormone [12]. Atrial natriuretic peptide is present in the ventricular tissue of fetuses and neonates, in hypertrophied ventricles as well as in low concentrations in normal ventricles. However, the atria are the main source in the adult normal heart [7].

A separate natriuretic 32-amino-acid peptide pro-ANP fragment called urodilatin has been identified in human urine [13]. Plasma levels of urodilatin are negligible since it is produced within the kidney by a unique processing pathway. Distal nephron cells have been shown to secrete an ANP pro-hormone that could be the precursor of urodilatin. Urodilatin appears to be more resistant to neutral endopeptidases (NEP). Its role in heart failure, if any, is still not very clear [14].

2.2. Brain natriuretic peptide
Human BNP is encoded by a single copy gene consisting of three exons and two introns. Its mRNA has a characteristic feature by virtue of the presence of four AUUUAA repeat sequences within the 3' untranslated region that is considered to produce mRNA stability [8].

The post-translational processing of the BNP precursor gene is different from that of the human ANP precursor. Regulation of ANP seems to occur at the level of release from storage granules whereas BNP regulation takes place during gene expression [15]. Human brain natriuretic peptide is produced in bursts in the heart as 108 amino acid precursor (pro-BNP) [16]. Further processing releases a mature biologically active 32-amino-acid molecule BNP, which corresponds to the C-terminal sequence of the human BNP precursor and a 76 aminoacid N-terminal fragment (NT-proBNP) (Fig. 1) [17]. The biologically active BNP, the intact 108 amino acid proBNP and the remaining part of the pro-hormone NT-proBNP all circulate in the plasma and can be measured by immunoassay. Circulating BNP consists of 32 amino acids with a characteristic ring closed by a disulfide bond between two cysteine residues, an amino-terminal tail of nine amino acids, and a carboxyl-terminal tail of six amino-acids [8]. Although atrial and to a greater extent ventricular cardiomyocytes constitute the major source of BNP related peptides, recent data demonstrated that other cells such as cardiac fibroblasts can also produce BNP. In addition, various neurohormones may stimulate cardiac BNP production in interplay between different cardiac cell types.

View larger version (8K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 1 Structure of brain natriuretic peptide and its activation site.

 
In normal subjects the plasma concentrations of NT-proBNP and BNP are similar. Both are continuously released from the heart and are detectable at picomolar concentrations in the venous blood of healthy subjects. With a half life of approximately 22 min in blood [8], BNP can accurately reflect pulmonary capillary wedge pressure changes every 2 h. The plasma half-life of NT-proBNP is 120 min suggesting that meaningful changes in hemodynamics could be reflected by this test approximately every 12 h [18]. However, in patients with left ventricular dysfunction NT-proBNP levels rise more than BNP with plasma concentration 2–10 times higher than BNP. The exact mechanism responsible for this relative change in peptide levels remains undetermined. Shifts in cardiac secretion and/or clearance mechanisms are thought to play a role. Taken together the greater rise in NT-proBNP during heart failure may make it a better marker as compared to BNP [19].

The correlation between BNP and estimated glomerular filtration rate is approximately r=–0.20. This implies a higher cutoff for BNP in the diagnosis of CHF when kidney disease advances. Nevertheless using this approach, BNP maintains a high level of diagnostic utility [20]. NT-proBNP has a stronger correlation with eGFR of approximately r=–0.60, and is influenced by the normal age-related decline in renal function. Therefore, below an eGFR of 60 ml/min/1.73 m², which is common in the elderly, the cutoff of NT-proBNP for detecting CHF might be less accurate [21]. This tight relationship to renal function has led some investigators to suggest that NT-proBNP reflects cardiorenal instead of cardiac function [18].

2.3. C-type natriuretic peptide
A third natriuretic peptide, C-type NP is expressed primarily in the central nervous system and vascular tissues and, unlike ANP and BNP, is nearly non-existent in cardiac tissue [22]. The gene encoding CNP is localized to human chromosome 2 and contains two exons separated by an intron. The NPCC gene encodes a 126-residu CNP precursor peptide pro-CNP that is processed to generate 22- (CNP-22) and 53-amino acid peptides (CNP-53). CNP-22 is more widely and abundantly expressed and is more potent than C-53 peptide [7]. CNP has remarkable similarity to ANP in its amino acid sequence but lacks the Carboxy-terminal tail of ANP [23]. The low almost undetectable levels of CNP suggests that this peptide acts primarily as a neurotransmitter in a paracrine way [24], while ANP and BNP function more as true counter-regulatory hormones [25]. Nevertheless, CNP does play an important role in cardiovascular physiology as a potent vasorelaxant, as well as an inhibitor of vascular smooth muscle proliferation and endothelial cell migration [17]. Recent data also reported a lusitropic and negative inotropic effect of CNP infusion in isolated papillary muscle [26].

2.4. D-type natriuretic peptide
Dendroaspis natriuretic peptide (DNP), a 38-aminoacid peptide is the newest of the natriuretic peptides. It was isolated from the venom of the Green Mamba (Dendroaspis angusticeps) and has structural similarities to the three known human cardiac natriuretic peptides [27], It shares the characteristic 17-aminoacid disulfide ring with all natriuretic peptides but is structurally different in its N- and C-terminal regions. Human data about this NP are scarce: The gene for DNP has not been cloned neither in the snake nor in any mammal in contrast to the other natriuretic peptides. Recently, a ‘DNP-like’ peptide has been isolated from human plasma and human atria, yet conclusive evidence about its presence in man remains controversial. Some authors suggest DNP is a primitive, ancestral cardiac natriuretic peptide, an evolutionary precursor to ANP and BNP [10].

	3. Natriuretic peptide receptors

Top Abstract 1. Introduction 2. The natriuretic peptide... 3. Natriuretic peptide receptors 4. Clearance of natriuretic... 5. Regulation and induction... 6. Actions of the... 7. Conclusion References

 
The natriuretic peptides are ligands for three different cell surface receptors named natriuretic peptide receptor (NPR) A, NPR-B and NPR-C that mediate their physiological effects. Each of these receptors contains a single transmembrane domain and an extracellular binding domain [28].

Natriuretic peptide receptor A and B are structurally similar, with approximately 44% homology in the ligand-binding extracellular domain [29]. Although both receptors are found in the adrenal gland and the kidney, NPR-A is most abundant in large blood vessels in contrast to NPR-B that predominates in the brain, particularly in the pituitary gland [8]. ANP and BNP bind preferentially to NPR-A that dimerizes and uses a chloride ion to hold itself in the ‘open’ position. The receptor is linked to a cyclic guanylate monophosphate (c-GMP)-dependent signaling cascade that mediates most of its biological activity [24]. Mice lacking this functional NPR-A receptor exhibit hypertension, cardiac hypertrophy and dilatation and die suddenly before the age of 6 months [30].

The relatively low affinity of BNP for NPR-A with a potency approximately 10-fold lower than that of ANP [31], has led to the speculation that an additional BNP-specific guanylate cyclase receptor might play a role [26]. Of note in NPR-A knockout mice testis and adrenal glands retain significant high-affinity response to BNP that can only be accounted for by the presence of a novel receptor in these tissues that prefers BNP over ANP. Although the physiological significance and the biochemical components of this receptor remains to be established, its existence does reinforce the notion that ANP and BNP are likely to carry out at least some independent actions [26].

CNP does not act through NPR-A but selectively activates NPR-B a second guanylate cyclase receptor [26]. As previously mentioned, this receptor is similar to NPR-A. Nevertheless, it is only weakly sensitive to ANP and BNP [24].

In contrast to NPR-A and NPR-B the NPR-C is devoid of guanyl cyclase activity and contains 37 amino acid cytoplasmatic domain that contains a G protein-activating sequence [24]. They are the most widely and abundantly expressed natriuretic peptide receptors and are located in several tissues including vascular endothelium, smooth muscle, heart, adrenal glands and kidney [32]. As demonstrated by studies performed in NPR-C knockout mice, it serves as a clearance receptor for ANP, BNP and CNP [33]. All three natriuretic peptides bind to this receptor in the order of ANP>CNP>BNP [34], are internalized and enzymatically degraded, after which the C-receptor returns to the cell surface [7]. In addition, recent data indicate that the NPR-C alters target cell function through Gi protein-coupled inhibition of membrane adenylate cyclase activity [24].

The lower affinity of NPR-C for BNP with an interaction partly accounts for the longer plasma half-life of BNP as compared to ANP in man [24].

	4. Clearance of natriuretic peptides

Top Abstract 1. Introduction 2. The natriuretic peptide... 3. Natriuretic peptide receptors 4. Clearance of natriuretic... 5. Regulation and induction... 6. Actions of the... 7. Conclusion References

 
Although the rate of synthesis and release of natriuretic peptides is a major regulator of plasma concentrations, the rate of removal of the peptides from the circulation is also important [35]. The clearance involves two main pathways: enzymatic degradation by neutral endopeptidase and as previously mentioned receptor-mediated endocytosis followed by lysosomal degradation via the natriuretic peptide receptor C (or clearance receptor) (Fig. 2) [6]. Renal clearance plays a lesser role at least for active C-terminal peptides. NEP, a zinc metallopeptidase is widely distributed on the surface of endothelial cells, smooth-muscle cells, cardiac myocytes and fibroblasts and is particularly concentrated at the brush border membranes in the proximal tubule of the kidney [17]. It cleaves the natriuretic peptides and opens the ring structure, thus inactivating the peptides [8]. The NPR-C is the most widely and abundantly expressed natriuretic peptide receptor and is located in several tissues including vascular endothelium and smooth muscle, heart, adrenal gland and kidney [11,24]. NPR-C knockout mice are characterized by a prolonged half-life of exogenous ANP, mild reductions in blood pressure, increased basal bone turnover and bone deformities [33].

View larger version (18K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 2 Action of natriuretic peptides at target cells. GC means guanyl cyclase, NPR-A natriuretic peptide receptor A, NPR-B natriuretic peptide receptor B, NPR-C natriuretic peptide receptor C, NEP neutral endopeptidase, aldo aldosterone, OS orthosympathetic system.

 
The relative importance of these two mechanisms in the clearance is controversial. Although data from a number of studies in normal animals have demonstrated that NPR-C blockade has a greater effect on ANP clearance than do NEP inhibitors, others have demonstrated that the enzymatic and receptor clearance pathways equally contribute to the degradation of ANP and BNP at physiological plasma concentrations. In addition, it has been demonstrated that in states of chronically elevated endogenous natriuretic peptides, such as occurs in chronic heart failure, the clearance receptor may play a lesser role than NEP in the metabolism of the peptides because of higher receptor occupancy and species dependent ANP-mediated down-regulation of the NPR-C [36].

	5. Regulation and induction of ANP and BNP

Top Abstract 1. Introduction 2. The natriuretic peptide... 3. Natriuretic peptide receptors 4. Clearance of natriuretic... 5. Regulation and induction... 6. Actions of the... 7. Conclusion References

 
At the cellular level, stretch is the predominant stimulus controlling the release of BNP from the atria and the ventricles. The increased wall stretch acts directly or via local paracrine factors such as endothelin-1 [37], nitric oxide [17], and angiotensin II [38]. Apart from myocyte stretch other stimuli such as tachycardia [39] and glucocorticoids [40] contribute to the induction of cardiac BNP mRNA in overt heart failure [17].

ANP is primarily released by increased atrial transmural pressure. The release of BNP is modulated by both pressure and volume overload as evidenced by the correlation between left-ventricular chamber size [41], left ventricular enddiastolic pressure [42]and plasma BNP concentration. Note, in vivo data demonstrated a slow ANP gene induction within days after the initiation of increased cardiac overload. In contrast there is a rapid ‘within hours’ activation of the BNP gene, whenever wall stretch increases [43]. The slow induction of ANP allows storage of ANP in granules and periodical release from ANP out of these granules [44]. Because of the high turnover of the BNP messenger RNA, BNP cannot be stored but is released in bursts [45]. Experimental data suggest that upregulation of cardiac ANP is less dependent on the severity of heart failure; Indeed ANP mRNA is already induced in compensated heart failure when hypertrophy is present but LVEDP is still normal. In contrast BNP mRNA is only induced in heart failure when LVEDP is elevated [46]. Taken together these data not only give rise to the concept of BNP as an emergency hormone but also point toward the role of BNP as a marker for diagnosing the transition from compensated to decompensated heart failure [47].

	6. Actions of the natriuretic peptides

Top Abstract 1. Introduction 2. The natriuretic peptide... 3. Natriuretic peptide receptors 4. Clearance of natriuretic... 5. Regulation and induction... 6. Actions of the... 7. Conclusion References

 
6.1. Renal effects
At the level of the kidney, natriuretic peptides have multiple actions including stimulating natriuresis and diuresis. Atrial as well as brain natriuretic peptide exert their effects on the kidney primarily at the level of the glomerulus and collecting duct. In the glomerulus, it causes afferent arteriolar dilation together with efferent arteriolar vasoconstriction, thereby increasing the glomerular filtration rate [48]. In the collecting duct, it decreases sodium reabsorption, thereby increasing sodium excretion [49]. Both also inhibit the secretion of renin, angiotensin II and aldosterone [50]. Finally, mice over-expressing the BNP gene have a lower degree of glomerular hypertrophy and mesangial expansion with intraglomerular cells than wild mice in response to renal ablation [51].

6.2. Cardiovascular effects
Transgenic mice that overexpress BNP have a lower blood pressure and a lower peripheral vascular resistance than wild types [51]. This is chiefly caused by a primary shift of intravascular fluid into the extravascular compartment and an increase in venous capacitance with subsequent rise in natriuresis, resulting in a reduction of preload [20]. However, mice with targeted disruption of BNP develop multifocal fibrotic lesions in the cardiac ventricle in the absence of systemic hypertension or ventricular hypertrophy [52]. These observations together with the lusitropic effects of BNP infusion suggest BNP acts as a cardiomyocyte-derived antifibrotic factor in vivo that may function as a local regulator of ventricular remodeling [24].

Atrial as well as brain natriuretic peptides also have important central and peripheral sympathoinhibitory effects [7]. Damping of the baroreceptors, suppressed release of catecholamines from autonomic nerve findings and especially suppression of sympathetic outflow from the central nervous system all have been reported [17]. Finally, the activation threshold of vagal afferents is lowered thereby suppressing the reflex tachycardia and vasoconstriction that accompanies the reduction in preload [53].

	7. Conclusion

Top Abstract 1. Introduction 2. The natriuretic peptide... 3. Natriuretic peptide receptors 4. Clearance of natriuretic... 5. Regulation and induction... 6. Actions of the... 7. Conclusion References

 
The natriuretic peptide family plays a distinct physiological and pathophysiological role in cardiovascular control. It consists of at least four ligands, ANP, BNP, CNP DNP and three types of receptors expressed in target tissues with tissue specificity. By binding to all three classes of receptors the natriuretic peptides act in concert to regulate cardiovascular function. Because of its fast induction and specific expression in overt heart failure, BNP seems the most promising natriuretic peptide as a marker of LV dysfunction and makes it an important component of future cardiac care.

	References

Top Abstract 1. Introduction 2. The natriuretic peptide... 3. Natriuretic peptide receptors 4. Clearance of natriuretic... 5. Regulation and induction... 6. Actions of the... 7. Conclusion References

 

1. de Bold A.J., Borenstein H.B., Veress A.T., Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci (1981) 28:89–94.[CrossRef][Web of Science][Medline]
2. Sudoh T., Minamino N., Kangawa K., Matsuo H. Brain natriuretic peptide-32: N-terminal six amino acid extended form of brain natriuretic peptide identified in porcine brain. Biochem Biophys Res Commun (1988) 155:726–732.[CrossRef][Web of Science][Medline]
3. Dao Q., Krishnaswamy P., Kazanegra R., et al. Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. J Am Coll Cardiol (2001) 37:379–385.[Abstract/Free Full Text]
4. McCullough P.A., Nowak R.M., McCord J., et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from breathing not properly (BNP) multinational study. Circulation (2002) 106:416–422.[Abstract/Free Full Text]
5. Cheng V., Kazanagra R., Garcia A., et al. A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study. J Am Coll Cardiol (2001) 37:386–391.[Abstract/Free Full Text]
6. Nakao K., Ogawa Y., Suga S., Imura H. Molecular biology and biochemistry of the natriuretic peptide system. II: Natriuretic peptide receptors. J Hypertens (1992) 10:1111–1114.[CrossRef][Web of Science][Medline]
7. Levin E.R., Gardner D.G., Samson W.K. Natriuretic peptides. N Engl J Med (1998) 339:321–328.[Free Full Text]
8. Valli N., Gobinet A., Bordenave L. Review of 10 years of the clinical use of brain natriuretic peptide in cardiology. J Lab Clin Med (1999) 134:437–444.[CrossRef][Web of Science][Medline]
9. Tamura N., Ogawa Y., Yasoda A., Itoh H., Saito Y., Nakao K. Two cardiac natriuretic peptide genes (atrial natriuretic peptide and brain natriuretic peptide) are organized in tandem in the mouse and human genomes. J Mol Cell Cardiol (1996) 28:1811–1815.[CrossRef][Web of Science][Medline]
10. Richards A.M., Lainchbury J.G., Nicholls M.G., Cameron A.V., Yandle T.G. Dendroaspis natriuretic peptide: endogenous or dubious? Lancet (2002) 359:5–6.[CrossRef][Web of Science][Medline]
11. Espiner E.A., Richards A.M., Yandle T.G., Nicholls M.G. Natriuretic hormones. Endocrinol Metab Clin North Am (1995) 24:481–509.[Web of Science][Medline]
12. Vesely D.L., Douglass M.A., Dietz J.R., et al. Three peptides from the atrial natriuretic factor prohormone amino terminus lower blood pressure and produce diuresis, natriuresis, and/or kaliuresis in humans. Circulation (1994) 90:1129–1140.[Abstract/Free Full Text]
13. Schulz-Knappe P., Forssmann K., Herbst F., Hock D., Pipkorn R., Forssmann W.G. Isolation and structural analysis of ‘urodilatin’, a new peptide of the cardiodilatin-(ANP)-family, extracted from human urine. Klin Wochenschr (1988) 66:752–759.[CrossRef][Web of Science][Medline]
14. Ritter D., Chao J., Needleman P., Tetens E., Greenwald J.E. Localization, synthetic regulation, and biology of renal atriopeptin-like prohormone. Am J Physiol (1992) 263:F503–F509.[Web of Science][Medline]
15. Onuoha G.N., Nicholls D.P., Patterson A., Beringer T. Neuropeptide secretion in exercise. Neuropeptides (1998) 32:319–325.[CrossRef][Web of Science][Medline]
16. Yasue H., Yoshimura M., Sumida H., et al. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation (1994) 90:195–203.[Abstract/Free Full Text]
17. de Lemos J.A., McGuire D.K., Drazner M.H. B-type natriuretic peptide in cardiovascular disease. Lancet (2003) 362:316–322.[CrossRef][Web of Science][Medline]
18. McCullough P.A., Omland T., Maisel A.S. B-type natriuretic peptides: a diagnostic breakthrough for clinicians. Rev Cardiovasc Med (2003) 4:72–80.[Medline]
19. Hunt P.J., Richards A.M., Nicholls M.G., Yandle T.G., Doughty R.N., Espiner E.A. Immunoreactive amino-terminal pro-brain natriuretic peptide (NT-PROBNP): a new marker of cardiac impairment. Clin Endocrinol (Oxf) (1997) 47:287–296.[CrossRef][Medline]
20. Vesely D.L. Natriuretic peptides and acute renal failure. Am J Physiol Renal Physiol (2003) 285:F167–F177.[Abstract/Free Full Text]
21. McCullough P.A., Sandberg K.R. B-type natriuretic peptide and renal disease. Heart Fail Rev (2003) 8:355–358.[CrossRef][Web of Science][Medline]
22. Sudoh T., Minamino N., Kangawa K., Matsuo H. C-type natriuretic peptide (CNP): a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun (1990) 168:863–870.[CrossRef][Web of Science][Medline]
23. Tawaragi Y., Fuchimura K., Tanaka S., Minamino N., Kangawa K., Matsuo H. Gene and precursor structures of human C-type natriuretic peptide. Biochem Biophys Res Commun (1991) 175:645–651.[CrossRef][Web of Science][Medline]
24. Kone B.C. Molecular biology of natriuretic peptides and nitric oxide synthases. Cardiovasc Res (2001) 51:429–441.[Abstract/Free Full Text]
25. Barr C.S., Rhodes P., Struthers A.D. C-type natriuretic peptide. Peptides (1996) 17:1243–1251.[CrossRef][Web of Science][Medline]
26. Goy M.F., Oliver P.M., Purdy K.E., et al. Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide. Biochem J (2001) 358:379–387.[CrossRef][Web of Science][Medline]
27. Schweitz H., Vigne P., Moinier D., Frelin C., Lazdunski M. A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps). J Biol Chem (1992) 267:13 928–13 932.[Abstract/Free Full Text]
28. Porter J.G., Arfsten A., Fuller F., Miller J.A., Gregory L.C., Lewicki J.A. Isolation and functional expression of the human atrial natriuretic peptide clearance receptor cDNA. Biochem Biophys Res Commun (1990) 171:796–803.[CrossRef][Web of Science][Medline]
29. Koller K.J., Goeddel D.V. Molecular biology of the natriuretic peptides and their receptors. Circulation (1992) 86:1081–1088.[Abstract/Free Full Text]
30. Pandey K.N., Oliver P.M., Maeda N., Smithies O. Hypertension associated with decreased testosterone levels in natriuretic peptide receptor-A gene-knockout and gene-duplicated mutant mouse models. Endocrinology (1999) 140:5112–5119.[Abstract/Free Full Text]
31. Schulz S., Singh S., Bellet R.A., et al. The primary structure of a plasma membrane guanylate cyclase demonstrates diversity within this new receptor family. Cell (1989) 58:1155–1162.[CrossRef][Web of Science][Medline]
32. Maack T., Suzuki M., Almeida F.A., et al. Physiological role of silent receptors of atrial natriuretic factor. Science (1987) 238:675–678.[Abstract/Free Full Text]
33. Matsukawa N., Grzesik W.J., Takahashi N., et al. The natriuretic peptide clearance receptor locally modulates the physiological effects of the natriuretic peptide system. Proc Natl Acad Sci USA (1999) 96:7403–7408.[Abstract/Free Full Text]
34. Suga S., Nakao K., Hosoda K., et al. Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide. Endocrinology (1992) 130:229–239.[Abstract/Free Full Text]
35. Rademaker M.T., Charles C.J., Kosoglou T., et al. Clearance receptors and endopeptidase: equal role in natriuretic peptide metabolism in heart failure. Am J Physiol (1997) 273:H2372–H2379.[Web of Science][Medline]
36. Kishimoto I., Nakao K., Suga S., et al. Downregulation of C-receptor by natriuretic peptides via ANP-B receptor in vascular smooth muscle cells. Am J Physiol (1993) 265:H1373–H1379.[Web of Science][Medline]
37. Bruneau B.G., Piazza L.A., de Bold A.J. BNP gene expression is specifically modulated by stretch and ET-1 in a new model of isolated rat atria. Am J Physiol (1997) 273:H2678–H2686.[Web of Science][Medline]
38. Wiese S., Breyer T., Dragu A., et al. Gene expression of brain natriuretic peptide in isolated atrial and ventricular human myocardium: influence of angiotensin II and diastolic fiber length. Circulation (2000) 102:3074–3079.[Abstract/Free Full Text]
39. Riddervold F., Smiseth O.A., Hall C., Groves G., Risoe C. Rate-induced increase in plasma atrial natriuretic factor can occur independently of changes in atrial wall stretch. Am J Physiol (1991) 260:H1953–H1958.[Web of Science][Medline]
40. Nishimori T., Tsujino M., Sato K., Imai T., Marumo F., Hirata Y. Dexamethasone-induced up-regulation of adrenomedullin and atrial natriuretic peptide genes in cultured rat ventricular myocytes. J Mol Cell Cardiol (1997) 29:2125–2130.[CrossRef][Web of Science][Medline]
41. Qi W., Mathisen P., Kjekshus J., et al. Natriuretic peptides in patients with aortic stenosis. Am Heart J (2001) 142:725–732.[CrossRef][Web of Science][Medline]
42. Haug C., Metzele A., Kochs M., Hombach V., Grunert A. Plasma brain natriuretic peptide and atrial natriuretic peptide concentrations correlate with left ventricular end-diastolic pressure. Clin Cardiol (1993) 16:553–557.[Web of Science][Medline]
43. Hama N., Itoh H., Shirakami G., et al. Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation (1995) 92:1558–1564.[Abstract/Free Full Text]
44. Sumida H., Yasue H., Yoshimura M., et al. Comparison of secretion pattern between A-type and B-type natriuretic peptides in patients with old myocardial infarction. J Am Coll Cardiol (1995) 25:1105–1110.[Abstract]
45. Yasue H., Yoshimura M., Sumida H., et al. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation (1994) 90:195–203.[Abstract/Free Full Text]
46. Langenickel T., Pagel I., Hohnel K., Dietz R., Willenbrock R. Differential regulation of cardiac ANP and BNP mRNA in different stages of experimental heart failure. Am J Physiol Heart Circ Physiol (2000) 278:H1500–H1506.[Abstract/Free Full Text]
47. Yoshimura M., Yasue H., Okumura K., et al. Different secretion patterns of atrial natriuretic peptide and brain natriuretic peptide in patients with congestive heart failure. Circulation (1993) 87:464–469.[Abstract/Free Full Text]
48. Weidmann P., Hasler L., Gnadinger M.P., et al. Blood levels and renal effects of atrial natriuretic peptide in normal man. J Clin Invest (1986) 77:734–742.[Web of Science][Medline]
49. Zeidel M.L., Kikeri D., Silva P., Burrowes M., Brenner B.M. Atrial natriuretic peptides inhibit conductive sodium uptake by rabbit inner medullary collecting duct cells. J Clin Invest (1988) 82:1067–1074.[Web of Science][Medline]
50. Richards A.M., McDonald D., Fitzpatrick M.A., et al. Atrial natriuretic hormone has biological effects in man at physiological plasma concentrations. J Clin Endocrinol Metab (1988) 67:1134–1139.[Abstract/Free Full Text]
51. Kasahara M., Mukoyama M., Sugawara A., et al. Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation. J Am Soc Nephrol (2000) 11:1691–1701.[Abstract/Free Full Text]
52. Tamura N., Ogawa Y., Chusho H., et al. Cardiac fibrosis in mice lacking brain natriuretic peptide. Proc Natl Acad Sci USA (2000) 97:4239–4244.[Abstract/Free Full Text]
53. Schultz H.D., Gardner D.G., Deschepper C.F., Coleridge H.M., Coleridge J.C. Vagal C-fiber blockade abolishes sympathetic inhibition by atrial natriuretic factor. Am J Physiol (1988) 255:R6–R13.[Web of Science][Medline]

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				L. A. Bockeria, O. L. Bockeria, and U. A. Kolesnikova eComment: Re: Brain natriuretic peptide a predictive marker in cardiac surgery Interactive CardioVascular and Thoracic Surgery, October 1, 2009; 9(4): 666 - 666. [Full Text] [PDF]

				R. Tagore, L. H. Ling, H. Yang, H.-Y. Daw, Y.-H. Chan, and S. K. Sethi Natriuretic Peptides in Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., November 1, 2008; 3(6): 1644 - 1651. [Abstract] [Full Text] [PDF]

				J. Madaric, M. Vanderheyden, C. Van Laethem, K. Verhamme, A. Feys, M. Goethals, S. Verstreken, P. Geelen, M. Penicka, B. De Bruyne, et al. Early and late effects of cardiac resynchronization therapy on exercise-induced mitral regurgitation: relationship with left ventricular dyssynchrony, remodelling and cardiopulmonary performance Eur. Heart J., September 1, 2007; 28(17): 2134 - 2141. [Abstract] [Full Text] [PDF]

				K.-S. Spanaus, F. Kronenberg, E. Ritz, R. Schlapbach, D. Fliser, M. Hersberger, B. Kollerits, P. Konig, A. von Eckardstein, and for the Mild-to-Moderate Kidney Disease Study Grou B-Type Natriuretic Peptide Concentrations Predict the Progression of Nondiabetic Chronic Kidney Disease: The Mild-to-Moderate Kidney Disease Study Clin. Chem., July 1, 2007; 53(7): 1264 - 1272. [Abstract] [Full Text] [PDF]

				R. Carrillo-Jimenez, S. Borzak, and C. H. Hennekens Brain Natriuretic Peptide: Clinical and Research Challenges Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2007; 12(2): 85 - 88. [Abstract] [PDF]

				B. Naegeli, D. J. Kurz, D. Koller, E. Straumann, M. Furrer, D. Maurer, E. Minder, and O. Bertel Single-chamber ventricular pacing increases markers of left ventricular dysfunction compared with dual-chamber pacing Europace, March 1, 2007; 9(3): 194 - 199. [Abstract] [Full Text] [PDF]

				T. W. Vogelsang, C. C. Yoshiga, M. Hojgaard, A. Kjaer, J. Warberg, N. H. Secher, and S. Volianitis The plasma atrial natriuretic peptide response to arm and leg exercise in humans: effect of posture Exp Physiol, July 1, 2006; 91(4): 765 - 771. [Abstract] [Full Text] [PDF]

				A. E. Malavazos, L. Morricone, A. Marocchi, F. Ermetici, B. Ambrosi, and M. M. Corsi N-terminal pro-B-type natriuretic Peptide and echocardiographic abnormalities in severely obese patients: correlation with visceral fat. Clin. Chem., June 1, 2006; 52(6): 1211 - 1213. [Full Text] [PDF]

				A Verma, F Kilicaslan, D O Martin, S Minor, R Starling, N F Marrouche, S Almahammed, O M Wazni, S Duggal, R Zuzek, et al. Preimplantation B-type natriuretic peptide concentration is an independent predictor of future appropriate implantable defibrillator therapies Heart, February 1, 2006; 92(2): 190 - 195. [Abstract] [Full Text] [PDF]

				I. Brandt, A.-M. Lambeir, J.-M. Ketelslegers, M. Vanderheyden, S. Scharpe, and I. De Meester Dipeptidyl-Peptidase IV Converts Intact B-Type Natriuretic Peptide into Its des-SerPro Form Clin. Chem., January 1, 2006; 52(1): 82 - 87. [Abstract] [Full Text] [PDF]

				S. R. Das, M. H. Drazner, D. L. Dries, G. L. Vega, H. G. Stanek, S. M. Abdullah, R. M. Canham, A. K. Chung, D. Leonard, F. H. Wians Jr, et al. Impact of Body Mass and Body Composition on Circulating Levels of Natriuretic Peptides: Results From the Dallas Heart Study Circulation, October 4, 2005; 112(14): 2163 - 2168. [Abstract] [Full Text] [PDF]

				M. Lafontan, C. Moro, C. Sengenes, J. Galitzky, F. Crampes, and M. Berlan An Unsuspected Metabolic Role for Atrial Natriuretic Peptides: The Control of Lipolysis, Lipid Mobilization, and Systemic Nonesterified Fatty Acids Levels in Humans Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2032 - 2042. [Abstract] [Full Text] [PDF]

				F. S. Apple, M. Panteghini, J. Ravkilde, J. Mair, A. H.B. Wu, J. Tate, F. Pagani, R. H. Christenson, A. S. Jaffe, and on Behalf of the Committee on Standardization of M Quality Specifications for B-Type Natriuretic Peptide Assays Clin. Chem., March 1, 2005; 51(3): 486 - 493. [Abstract] [Full Text] [PDF]

				M. Vanderheyden, M. Goethals, S. Verstreken, B. De Bruyne, K. Muller, E. Van Schuerbeeck, and J. Bartunek Wall stress modulates brain natriuretic peptide production in pressure overload cardiomyopathy J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2349 - 2354. [Abstract] [Full Text] [PDF]

				S. Bruins, M. R. Fokkema, J. W.P. Romer, M. J.L. DeJongste, F. P.L. van der Dijs, J. M.W. van den Ouweland, and F. A.J. Muskiet High Intraindividual Variation of B-Type Natriuretic Peptide (BNP) and Amino-Terminal proBNP in Patients with Stable Chronic Heart Failure Clin. Chem., November 1, 2004; 50(11): 2052 - 2058. [Abstract] [Full Text] [PDF]

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Disclaimer Google Scholar Articles by Vanderheyden, M. Articles by Goethals, M. Search for Related Content PubMed PubMed Citation Articles by Vanderheyden, M. Articles by Goethals, M. Social Bookmarking          What's this?

Online ISSN 1879-0844 - Print ISSN 1388-9842

Copyright © 2009 European Society of Cardiology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics