Presence of Dendroaspis Natriuretic Peptide-Like Immunoreactivity in Human Plasma and Its Increase During Human Heart Failure

Schirger, John A.; Heublein, Denise M.; Chen, Horng H.; Lisý, Ondřej; Jougasaki, Michihisa; Wennberg, Paul W.; Burnett, John C.

doi:10.4065/74.2.126

Cited by 115 publications

(71 citation statements)

References 9 publications

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“…ANP and BNP exist in amphibians and mammals, while birds apparently lack ANP [see Takei (Takei, 2000) for references] but possess an NP highly expressed in the kidney [renal NP (RNP)] (Trajanowska et al, 2007;Trajanowska and Donald, 2008). Mammals and reptiles also express DNP (Schirger et al, 1999;Kim et al, 2004;Woodard et al, 2002).…”

Section: Np-npr System: Molecular and Evolutionary Strategiesmentioning

confidence: 99%

Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a ‘whip-brake’ system of the endocrine heart

Tota

Cerra

Gattuso

2010

Journal of Experimental Biology

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Summary In the past 50 years, extensive evidence has shown the ability of vertebrate cardiac non-neuronal cells to synthesize and release catecholamines (CA). This formed the mindset behind the search for the intrinsic endocrine heart properties, culminating in 1981 with the discovery of the natriuretic peptides (NP). CA and NP, co-existing in the endocrine secretion granules and acting as major cardiovascular regulators in health and disease, have become of great biomedical relevance for their potent diagnostic and therapeutic use. The concept of the endocrine heart was later enriched by the identification of a growing number of cardiac hormonal substances involved in organ modulation under normal and stress-induced conditions. Recently, chromogranin A (CgA), a major constituent of the secretory granules, and its derived cardio-suppressive and antiadrenergic peptides, vasostatin-1 and catestatin, were shown as new players in this framework, functioning as cardiac counter-regulators in ‘zero steady-state error’ homeostasis, particularly under intense excitatory stimuli, e.g. CA-induced myocardial stress. Here, we present evidence for the hypothesis that is gaining support, particularly among human cardiologists. The actions of CA, NP and CgA, we argue, may be viewed as a hallmark of the cardiac capacity to organize ‘whip-brake’ connection-integration processes in spatio-temporal networks. The involvement of the nitric oxide synthase (NOS)/nitric oxide (NO) system in this configuration is discussed. The use of fish and amphibian paradigms will illustrate the ways that incipient endocrine-humoral agents have evolved as components of cardiac molecular loops and important intermediates during evolutionary transitions, or in a distinct phylogenetic lineage, or under stress challenges. This may help to grasp the old evolutionary roots of these intracardiac endocrine/paracrine networks and how they have evolved from relatively less complicated designs. The latter can also be used as an intellectual tool to disentangle the experimental complexity of the mammalian and human endocrine hearts, suggesting future investigational avenues.

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Section: Np-npr System: Molecular and Evolutionary Strategiesmentioning

confidence: 99%

Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a ‘whip-brake’ system of the endocrine heart

Tota

Cerra

Gattuso

2010

Journal of Experimental Biology

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“…21 Although a DNP homolog has not yet been identified by bioinformatic analysis of the human genome, immunoreactivity (IR) to this peptide has been detected in human tissues, 22 whereas circulating levels have been demonstrated to correspond to the degree of HF. 23 The physiological function of DNP is similar to ANP, inducing natriuresis 24 and vasodilatation. 22 Interestingly, neutral endopeptidase 24.11(NEP) does not affect DNP-mediated effects in animals, 25 suggesting that DNP may have enhanced resistance to degradation.…”

mentioning

confidence: 99%

Novel Snake Venom Ligand Dendroaspis Natriuretic Peptide Is Selective for Natriuretic Peptide Receptor-A in Human Heart

Singh

Kuc

Maguire

et al. 2006

Circulation Research

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Abstract-The natriuretic peptides are considered to be cardioprotective; however, their receptors have not been identified in human myocardium using radiolabeled analogs. Dendroaspis natriuretic peptide (DNP) has been recently identified as a new member of this peptide family and is thought to be less susceptible to enzymatic degradation. Therefore, we have developed the novel radiolabeled analog [ 125 I]-DNP and used this to localize high-affinity (K D ϭ0.2 nmol/L), saturable, specific binding sites in adult human heart (nϭ6) and coronary artery (nϭ8). In competition binding experiments, atrial natriuretic peptide and brain type natriuretic peptide had greater affinity for [125 I]-DNP binding sites than C-type natriuretic peptide and the natriuretic peptide receptor (NPR)-C ligand, cANF. This rank order of potency suggested binding of [125 I]-DNP was specific to NPR-A. Messenger RNA encoding NPR-A was identified in left ventricle and coronary artery smooth muscle, and expression was confirmed by immunocytochemical studies at the protein level. In addition, fluorescence dual labeling immunocytochemistry localized NPR-A protein to cardiomyocytes, endocardial endothelial cells, and smooth muscle of intramyocardial vessels. Importantly, we demonstrated a significant downregulation in the density of NPR-A in heart and coronary artery of patients with ischemic heart disease that may explain, in part, the attenuated natriuretic peptide response reported in this patient group. Key Words: Dendroaspis natriuretic peptide Ⅲ heart failure Ⅲ downregulation Ⅲ natriuretic peptide receptor-A T he heart contributes to the regulation of cardiovascular homeostasis by synthesizing and secreting 2 natriuretic peptide hormones: atrial natriuretic peptide (ANP) 1 and brain type natriuretic peptide (BNP). 2 ANP and BNP protect the heart from volume overload by inducing potent natriuresis, diuresis, and vasodilatation. Other cardiac protective roles involve attenuation of cardiac hypertrophy, suppression of both the renin-angiotensin-aldosterone system and sympathetic nervous system activity, while enhancing vagal reflexes. 3 These effects result in decreased preload and after-load to the heart, which further prevents the development of pathologic cardiac hypertrophy and the progression to heart failure (HF).In situations of cardiac stress, the heart responds by increasing the secretion of natriuretic peptides from the ventricles, resulting in significantly enhanced circulating levels of ANP 4 and BNP. 5 The plasma concentration of these peptides, in particular BNP, has been strongly associated with the degree of left ventricular dysfunction and is being used as a diagnostic and prognostic marker for HF. 6,7 Despite the increase in circulating ANP and BNP, the natriuretic, diuretic, and vasodilatory efficacy of these peptides are dramatically reduced in HF. 8,9 This may reflect increased metabolism or clearance of natriuretic peptides from circulation and/or downregulation of functional natriuretic peptide receptors (NPRs), although o...

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“…2,3 We have reported that DNP immunoreactivity is present in human plasma and atrial myocardium and is elevated in the plasma of humans with CHF. 4 The therapeutic potential of DNP is supported by recent studies in normal animals in which intravenous administration of synthetic DNP had potent natriuretic and diuretic properties, which were associated with marked increases in plasma and urinary cGMP. 5 DNP, in contrast to the other known natriuretic peptides, may have unique characteristics that support its development as a new intravenous agent for acutely decompensated severe CHF.…”

mentioning

confidence: 99%

“…These properties include an extended C-terminus, which may result in greater resistance to neutral endopeptidase (NEP), the degradative enzyme of the natriuretic peptides. 6 DNP also has greater potency in cGMP generation compared with ANP, BNP, or CNP 7 and demonstrates a lack of marked plasma elevation in CHF, 4 which could have relevance to receptor sensitivity. However, to date, the biological actions of synthetic DNP in heart failure are unknown.…”

mentioning

confidence: 99%

Therapeutic Actions of a New Synthetic Vasoactive and Natriuretic Peptide, Dendroaspis Natriuretic Peptide, in Experimental Severe Congestive Heart Failure

et al. 2001

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Abstract-Dendroaspis natriuretic peptide (DNP), a recently discovered peptide, shares structural similarity to the other known natriuretic peptides, ANP, BNP, and CNP. Studies have reported that DNP is present in human and canine plasma and atrial myocardium and increased in plasma of humans with congestive heart failure (CHF). In addition, synthetic DNP is markedly natriuretic and diuretic and is a potent activator of cGMP in normal animals. To date, the ability of synthetic DNP to improve cardiorenal function in experimental CHF is unknown. Synthetic DNP was administered intravenously at 10 and 50 ng · kg Ϫ1 · min Ϫ1 in dogs (nϭ7) with severe CHF induced by rapid ventricular pacing for 10 days at 245 bpm. In addition, we determined endogenous DNP in normal (nϭ4) and failing (nϭ4) canine atrial and ventricular myocardium. We report that administration of synthetic DNP in experimental severe CHF has beneficial cardiovascular, renal, and humoral properties. First, DNP in CHF decreased cardiac filling pressures, specifically right atrial pressure and pulmonary capillary wedge pressure. Second, DNP increased glomerular filtration rate in association with natriuresis and diuresis despite a reduction in mean arterial pressure. Third, DNP increased plasma and urinary cGMP and suppressed plasma renin activity. Fourth and finally, we report that DNP immunoreactivity is present in canine atrial and ventricular myocardium and increased in CHF. These studies report the acute intravenous actions of synthetic DNP in experimental severe CHF and suggest that on the basis of its beneficial properties, DNP may have potential as a new intravenous agent for the treatment of decompensated CHF. Key Words: heart failure Ⅲ natriuretic peptides Ⅲ cyclic guanosine monophosphate Ⅲ renin Ⅲ endopeptidase A s the prevalence of congestive heart failure (CHF) has increased during the past decade, so has hospitalization for acutely decompensated CHF. 1 This has resulted in a continued search for new therapeutic agents to treat CHF, including intravenous agents for acutely decompensated CHF, which is characterized by markedly elevated cardiac filling pressure with pulmonary congestion, impaired glomerular filtration rate (GFR) with sodium retention, and activation of the renin-angiotensin-aldosterone system.Recently, a new member of the natriuretic peptide family, Dendroaspis natriuretic peptide (DNP), has been reported. 2 DNP, originally isolated from the venom of the Dendroaspis angusticeps (green mamba snake), is a 38-amino-acid peptide that contains a 17-amino-acid disulfide ring structure with 15-residue C-terminal extension. This peptide, which shares structural similarity to atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), potently vasorelaxes isolated precontracted rodent aorta and canine coronary arteries and augments the formation of 3Ј,5Ј cyclic guanosine monophosphate (cGMP) in aortic endothelial and smooth muscle cells. 2,3 We have reported that DNP immunoreactivity is present...

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Presence of Dendroaspis Natriuretic Peptide-Like Immunoreactivity in Human Plasma and Its Increase During Human Heart Failure

Cited by 115 publications

References 9 publications

Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a ‘whip-brake’ system of the endocrine heart

Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a ‘whip-brake’ system of the endocrine heart

Novel Snake Venom Ligand Dendroaspis Natriuretic Peptide Is Selective for Natriuretic Peptide Receptor-A in Human Heart

Therapeutic Actions of a New Synthetic Vasoactive and Natriuretic Peptide, Dendroaspis Natriuretic Peptide, in Experimental Severe Congestive Heart Failure

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