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Handbook of Experimental Pharmacology 2009Natriuretic peptides are a family of three structurally related hormone/ paracrine factors. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are... (Review)
Review
Natriuretic peptides are a family of three structurally related hormone/ paracrine factors. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are secreted from the cardiac atria and ventricles, respectively. ANP signals in an endocrine and paracrine manner to decrease blood pressure and cardiac hypertrophy. BNP acts locally to reduce ventricular fibrosis. C-type natriuretic peptide (CNP) primarily stimulates long bone growth but likely serves unappreciated functions as well. ANP and BNP activate the transmembrane guanylyl cyclase, natriuretic peptide receptor-A (NPR-A). CNP activates a related cyclase, natriuretic peptide receptor-B (NPR-B). Both receptors catalyze the synthesis of cGMP, which mediates most known effects of natriuretic peptides. A third natriuretic peptide receptor, natriuretic peptide receptor-C (NPR-C), clears natriuretic peptides from the circulation through receptor-mediated internalization and degradation. However, a signaling function for the receptor has been suggested as well. Targeted disruptions of the genes encoding all natriuretic peptides and their receptors have been generated in mice, which display unique physiologies. A few mutations in these proteins have been reported in humans. Synthetic analogs of ANP (anaritide and carperitide) and BNP (nesiritide) have been investigated as potential therapies for the treatment of decompensated heart failure and other diseases. Anaritide and nesiritide are approved for use in acute decompensated heart failure, but recent studies have cast doubt on their safety and effectiveness. New clinical trials are examining the effect of nesiritide and novel peptides, like CD-NP, on these critical parameters. In this review, the history, structure, function, and clinical applications of natriuretic peptides and their receptors are discussed.
Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; History, 20th Century; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Receptors, Atrial Natriuretic Factor
PubMed: 19089336
DOI: 10.1007/978-3-540-68964-5_15 -
International Journal of Molecular... Apr 2019Currently, brain natriuretic peptide (BNP) and -terminal proBNP (NT-proBNP) are widely used as diagnostic biomarkers for heart failure (HF) and cardiac dysfunction in... (Review)
Review
Currently, brain natriuretic peptide (BNP) and -terminal proBNP (NT-proBNP) are widely used as diagnostic biomarkers for heart failure (HF) and cardiac dysfunction in clinical medicine. They are also used as postmortem biomarkers reflecting cardiac function of the deceased before death in forensic medicine. Several previous studies have reviewed BNP and NT-proBNP in clinical medicine, however, few articles have reviewed their application in forensic medicine. The present article reviews the biological features, the research and application status, and the future research prospects of BNP and NT-proBNP in both clinical medicine and forensic medicine, thereby providing valuable assistance for clinicians and forensic pathologists.
Topics: Animals; Biomarkers; Diagnosis; Forensic Medicine; Gene Expression Regulation; Heart Failure; Heart Function Tests; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proteolysis; Severity of Illness Index; Signal Transduction; Translational Research, Biomedical
PubMed: 31013779
DOI: 10.3390/ijms20081820 -
European Journal of Heart Failure May 2023Natriuretic peptides, brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are globally and most often used for...
Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society.
Natriuretic peptides, brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are globally and most often used for the diagnosis of heart failure (HF). In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor-neprilysin inhibitors (ARNIs), the use of natriuretic peptides as therapeutic agents has grown in importance. The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up-to-date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptide-guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions.
Topics: Humans; Biomarkers; Cardiology; Heart Failure; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Prognosis
PubMed: 37098791
DOI: 10.1002/ejhf.2848 -
Current Heart Failure Reports Sep 2014Nesiritide and dopamine have been recognized for some time as potential renal adjunct therapies in the management of patients with acute heart failure (AHF). Several... (Review)
Review
Nesiritide and dopamine have been recognized for some time as potential renal adjunct therapies in the management of patients with acute heart failure (AHF). Several studies have yielded conflicting evidence of the efficacy of both medications in enhancing the renal function of patients with AHF. The Renal Optimization Strategies Evaluation (ROSE) study was a multicenter double-blind placebo controlled trial designed to assess the potential renoprotective effects of low-dose nesiritide and dopamine in AHF patients with renal dysfunction. This article will focus on previous research, summary of results, and lessons learned from the ROSE-AHF trial as well as future directions for clinical research and applications.
Topics: Acute Kidney Injury; Disease Progression; Dose-Response Relationship, Drug; Heart Failure; Humans; Natriuretic Agents; Natriuretic Peptide, Brain; Stroke Volume; Treatment Outcome
PubMed: 24966060
DOI: 10.1007/s11897-014-0208-6 -
Redox Biology Jun 2023Brain natriuretic peptide (BNP) belongs to the family of natriuretic peptides, which are responsible for a wide range of actions. Diabetic cardiomyopathy (DCM) is often...
Brain natriuretic peptide (BNP) belongs to the family of natriuretic peptides, which are responsible for a wide range of actions. Diabetic cardiomyopathy (DCM) is often associated with increased BNP levels. This present research intends to explore the role of BNP in the development of DCM and the underlying mechanisms. Diabetes was induced in mice using streptozotocin (STZ). Primary neonatal cardiomyocytes were treated with high glucose. It was found that the levels of plasma BNP started to increase at 8 weeks after diabetes, which preceded the development of DCM. Addition of exogenous BNP promoted Opa1-mediated mitochondrial fusion, inhibited mitochondrial oxidative stress, preserved mitochondrial respiratory capacity and prevented the development of DCM, while knockdown of endogenous BNP exacerbated mitochondrial dysfunction and accelerated DCM. Opa1 knockdown attenuated the aforementioned protective action of BNP both in vivo and in vitro. BNP-induced mitochondrial fusion requires the activation of STAT3, which facilitated Opa1 transcription by binding to its promoter regions. PKG, a crucial signaling biomolecule in the BNP signaling pathway, interacted with STAT3 and induced its activation. Knockdown of NPRA (the receptor of BNP) or PKG blunted the promoting effect of BNP on STAT3 phosphorylation and Opa1-mediated mitochondrial fusion. The results of this study demonstrate for the first time that there is a rise in BNP during the early stages of DCM as a compensatory protection mechanism. BNP is a novel mitochondrial fusion activator in protecting against hyperglycemia-induced mitochondrial oxidative injury and DCM through the activation of NPRA-PKG-STAT3-Opa1 signaling pathway.
Topics: Animals; Mice; Diabetes Mellitus; Diabetic Cardiomyopathies; Mitochondrial Dynamics; Myocytes, Cardiac; Natriuretic Peptide, Brain; Signal Transduction; Cyclic GMP-Dependent Protein Kinases
PubMed: 37116257
DOI: 10.1016/j.redox.2023.102702 -
International Journal of Molecular... Aug 2019Atrial natriuretic peptide (ANP) is a cardiac hormone belonging to the family of natriuretic peptides (NPs). ANP exerts diuretic, natriuretic, and vasodilatory effects... (Review)
Review
Atrial natriuretic peptide (ANP) is a cardiac hormone belonging to the family of natriuretic peptides (NPs). ANP exerts diuretic, natriuretic, and vasodilatory effects that contribute to maintain water-salt balance and regulate blood pressure. Besides these systemic properties, ANP displays important pleiotropic effects in the heart and in the vascular system that are independent of blood pressure regulation. These functions occur through autocrine and paracrine mechanisms. Previous works examining the cardiac phenotype of loss-of-function mouse models of ANP signaling showed that both mice with gene deletion of ANP or its receptor natriuretic peptide receptor A (NPR-A) developed cardiac hypertrophy and dysfunction in response to pressure overload and chronic ischemic remodeling. Conversely, ANP administration has been shown to improve cardiac function in response to remodeling and reduces ischemia-reperfusion (I/R) injury. ANP also acts as a pro-angiogenetic, anti-inflammatory, and anti-atherosclerotic factor in the vascular system. Pleiotropic effects regarding brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were also reported. In this review, we discuss the current evidence underlying the pleiotropic effects of NPs, underlying their importance in cardiovascular homeostasis.
Topics: Animals; Cardiovascular System; Humans; Myocytes, Cardiac; Natriuretic Peptide, Brain; Natriuretic Peptides; Reperfusion Injury; Vascular Remodeling; Ventricular Remodeling
PubMed: 31398927
DOI: 10.3390/ijms20163874 -
Journal of Cellular and Molecular... 2007The natriuretic peptides are a family of related hormones that play a crucial role in cardiovascular and renal homeostasis. They have recently emerged as potentially... (Review)
Review
The natriuretic peptides are a family of related hormones that play a crucial role in cardiovascular and renal homeostasis. They have recently emerged as potentially important clinical biomarkers in heart failure. Natriuretic peptides, particularly brain natriuretic peptide (BNP) and the inactive N-terminal fragment of BNP, NT-proBNP, that has an even greater half-life than BNP, are elevated in heart failure and therefore considered to be excellent predictors of disease outcome. Nesiritide, a recombinant human BNP, has been shown to provide symptomatic and haemodynamic improvement in acute decompensated heart failure, although recent reports have suggested an increased short-term risk of death with nesiritide use. This review article describes: the current use of BNP and its inactive precursor NT-proBNP in diagnosis, screening, prognosis and monitoring of therapy for congestive heart failure, the renoprotective actions of natriuretic peptides after renal failure and the controversy around the therapeutic use of the recombinant human BNP nesiritide.
Topics: Acute Kidney Injury; Animals; Biomarkers; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides
PubMed: 18205700
DOI: 10.1111/j.1582-4934.2007.00125.x -
Emergencias : Revista de La Sociedad... Oct 2019
Topics: Humans; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments
PubMed: 31625317
DOI: No ID Found -
Current Heart Failure Reports Dec 2017Heart failure (HF) continues to be a public health burden despite advances in therapy, and the natriuretic peptide (NP) system is clearly of critical importance in this... (Review)
Review
PURPOSE OF REVIEW
Heart failure (HF) continues to be a public health burden despite advances in therapy, and the natriuretic peptide (NP) system is clearly of critical importance in this setting, spawning valuable diagnostic and prognostic testing, such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), as well as current and future therapeutics, including recombinant natriuretic peptides (e.g., carperitide, nesiritide) and recently sacubitril, which inhibits the key clearance mechanism for NPs. This article intends to summarize the existing evidence for the role of NP system genetic variation on cardiovascular phenotypes relevant to HF with particular focus on the potential impact on pharmacologic therapies.
RECENT FINDINGS
Several genes in NP system have been interrogated, in many cases genetic variation impacting protein quantity and function or related disease states. Recent data supports genetic variants potentially impacting pharmacokinetics or dynamics of medications targeting the pathway. Growing evidence indicates the importance of genetic variation to the functioning of the NP system and its pharmacologic manipulation.
Topics: Biomarkers; Genotype; Heart Failure; Humans; Natriuretic Peptide, Brain; Polymorphism, Genetic; Prognosis
PubMed: 29075957
DOI: 10.1007/s11897-017-0365-5 -
BMJ Open Jan 2016Current evidence suggests that nesiritide may have effects on renal function and decrease the incidence of mortality. However, a clear superiority using nesiritide in... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
Current evidence suggests that nesiritide may have effects on renal function and decrease the incidence of mortality. However, a clear superiority using nesiritide in terms of renal toxicity and mortality in patients with heart failure was not consistently proven by previous studies. We performed a meta-analysis of all randomised trials to obtain the best estimates of efficacy and safety of nesiritide for the initial treatment of decompensated heart failure.
METHOD
We performed a meta-analysis of randomised trials of nesiritide in patients with decompensated heart failure (n=38,064 patients, in 22 trials). Two reviewers independently extracted data. Data on efficacy and safety outcomes were collected. We calculated pooled relatives risk (RRs), weighted mean difference and associated 95% CIs.
RESULTS
Compared with placebo, dobutamine and nitroglycerin, nesiritide indicated no increasing risk of total mortality. Compared with the combined control therapy, nesiritide was associated with non-significant differences in short-term mortality (RR 1.24; 95% CI 0.85 to 1.80; p=0.27), mid-term mortality (RR 0.86; 95% CI 0.60 to 1.24; p=0.42) and long-term mortality (RR 0.94; 95% CI 0.75 to 1.18; p=0.61). Nesiritide therapy increased the risk of hypotension (p<0.00 001) and bradycardia (p=0.02) when compared with control therapy. Compared with dobutamine or placebo therapy, no differences in serum creatinine, blood urea nitrogen and creatinine clearance, and no risk of the need for dialysis was observed in nesiritide therapy.
CONCLUSIONS
Our findings indicated that, in patients with heart failure, nesiritide was not associated with the risk of mortality. However, it increased the risk of cardiovascular adverse events. The change of serum creatinine and creatinine clearance had no significant difference, and no risk of the need for dialysis was observed after low-dose nesiritide treatment.
Topics: Heart Failure; Humans; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Nitroglycerin; Randomized Controlled Trials as Topic; Treatment Outcome; Vasodilator Agents
PubMed: 26739721
DOI: 10.1136/bmjopen-2015-008545