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1.
Chronic heart failure as a state of reduced effectiveness of the natriuretic peptide system: implications for therapy.
Díez, J
European journal of heart failure. 2017;(2):167-176
Abstract
Natriuretic peptides (NPs) promote diuresis, natriuresis and vasodilation in early chronic heart failure (CHF), countering renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) overstimulation. Despite dramatic increases in circulating NP concentrations as CHF progresses, their effects become blunted. Increases in diuresis, natriuresis, and vasodilation after administration of exogenous atrial (ANP) or brain (BNP) natriuretic peptides are attenuated in patients with advanced CHF compared with controls. Several major factors may account for the reduced effectiveness of the natriuretic peptide system (NPS) in CHF. First, there is reduced availability of active forms of NPs, namely BNP. Second, target organ responsiveness becomes diminished. Third, the counter-regulatory hormones of the RAAS and SNS, and endothelin-1 become over-activated. Therefore, pharmacological approaches to enhance the functional effectiveness of the NPS in CHF have been explored in recent years. In terms of clinical outcomes, studies of synthetic BNP, or of neprilysin inhibitors alone or associated with an angiotensin converting enzyme inhibitor, have been controversial for several reasons. Recently, however, encouraging results have been obtained with the angiotensin receptor neprilysin inhibitor sacubitril/valsartan. The available data show that treatment with sacubitril/valsartan is associated with increased levels of NPs and their intracellular mediator cyclic guanosine monophosphate, suggesting improved functional effectiveness of the NPS, in addition to beneficial effects on mortality and morbidity outcomes. Therefore, combined targeting of the NPS and RAAS with sacubitril/valsartan emerges as the current optimal approach for redressing the neurohormonal imbalance in CHF.
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2.
Atrial natriuretic peptides in plasma.
Goetze, JP, Hansen, LH, Terzic, D, Zois, NE, Albrethsen, J, Timm, A, Smith, J, Soltysinska, E, Lippert, SK, Hunter, I
Clinica chimica acta; international journal of clinical chemistry. 2015;:25-8
Abstract
Measurement of cardiac natriuretic peptides in plasma has gained a diagnostic role in the assessment of heart failure. Plasma measurement is though hampered by the marked instability of the hormones, which has led to the development of analyses that target N-terminal fragments from the prohormone. These fragments are stable in plasma and represent surrogate markers of the actual natriuretic hormone. Post-translational processing of the precursors, however, is revealing itself to be a complex event with new information still being reported on proteolysis, covalent modifications, and amino acid derivatizations. In this mini-review, we summarize measurement of the principal cardiac hormone, e.g. atrial natriuretic peptide (ANP) and its precursor fragments. We also highlight some of the analytical pitfalls and problems and the concurrent clinical "proof of concept". We conclude that biochemical research into proANP-derived peptides is still worthy of attention and that new biological insight may change our chemical perception of the markers.
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3.
Pro Atrial Natriuretic Peptide (1-30) and 6-keto PGF1α Activity Affects Na(+) Homeostasis in Non-modulating Hypertension.
Sanchez, RA, Gilbert, BH, Masnatta, L, Giannone, C, Pesiney, C, Ramirez, AJ
Current hypertension reviews. 2015;(1):30-7
Abstract
Non-modulating hypertension (NMHT) is a high renin subtype of salt sensitive hypertension, which fails to achieve renal vasodilatation and a correct Na(+) handling during sodium load. We investigate, in MHT and NMHT, the role of ANP, the renin-angiotensin system and PgI2, in the renal sodium handling mechanisms. After 10 days of low (20mmol.L) or after 72hs of high (250mmol.L) sodium intake, 13 NMHT (34±5y; 9 male) and 13 MHT (32±4y; 10male) were studied. Pro-ANP (1-30) PgI2, PRA and total exchangeable Na(+)24 (ENa(+)) were measured. Under low sodium intake, PRA (4.2±0.5ng.ml.h; p<0.05) and Pro-ANP (78.6±2pg/ml, p<0.05) were higher than in NMHT under (3.1±0.4ng.ml.h and 69.8±3 pg/ml). After 72h of high Na(+) intake, Pro-ANP (1-30) increased significantly only in MHT (82.1±3pg/ml, p<0.05). PgI2, under low sodium intake (1.83±0.2pg/24h), increased in MHT after 72h under high sodium (2.58±0.5pg/ 24h, p<0.02). Under low sodium diet, PgI2 (2.16±0.11pg/24h) was as higher in NMHT, as in MHT. After 72h under high Na+ intake, it failed to show any change (2.61±0.36 pg/24h; p=ns). A significant correlation between variations in ENa(+) and mean blood pressure (r=0.50, p<0.01), variations in Pro-ANP (1-30) values and ENa(+) in MHT (r=0.95; p<0.001) while a negative correlation between ENa(+) variations and ENa(+) (r=0.81, p<0.05) was observed in NMHT. ENa(+) variations were only significantly related to variations in FF in MHT. Thus, in NMHT, there is an unbalanced relationship between vasonstrictor and vasodilator mediators. From these, as an extrarenal homeostatic mediator, ANP seems to play an important role to compensate the altered renal sodium handling.
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4.
Atrial natriuretic peptide and renal dopaminergic system: a positive friendly relationship?
Choi, MR, Rukavina Mikusic, NL, Kouyoumdzian, NM, Kravetz, MC, Fernández, BE
BioMed research international. 2014;:710781
Abstract
Sodium metabolism by the kidney is accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Renal dopamine plays a central role in this interactive network. The natriuretic hormones, such as the atrial natriuretic peptide, mediate some of their effects by affecting the renal dopaminergic system. Renal dopaminergic tonus can be modulated at different steps of dopamine metabolism (synthesis, uptake, release, catabolism, and receptor sensitization) which can be regulated by the atrial natriuretic peptide. At tubular level, dopamine and atrial natriuretic peptide act together in a concerted manner to promote sodium excretion, especially through the overinhibition of Na+, K+-ATPase activity. In this way, different pathological scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome or hypertension, are associated with impaired action of renal dopamine and/or atrial natriuretic peptide, or as a result of impaired interaction between these two natriuretic systems. The aim of this review is to update and comment on the most recent evidences demonstrating how the renal dopaminergic system interacts with atrial natriuretic peptide to control renal physiology and blood pressure through different regulatory pathways.
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5.
Human atrial natriuretic peptide treatment for acute heart failure: a systematic review of efficacy and mortality.
Kobayashi, D, Yamaguchi, N, Takahashi, O, Deshpande, GA, Fukui, T
The Canadian journal of cardiology. 2012;(1):102-9
Abstract
BACKGROUND The objectives of this study were to assess the effect of human atrial natriuretic peptide (hANP) treatment on physiological parameters and mortality in acute heart failure. METHODS The MEDLINE (1966-2009), EMBASE (1980-2009), Cochrane Central Register of Controlled Trials (1991-2009), American College of Physicians Journal Club (1991), Ichushi (Japana Centra Revuo Medicina) (1983-2009), Cinni (NII Scholarly and Academic Information Navigator) (1959-2009), National Diet Library Online Public Access Catalog (1969-2009), Webcat Plus (Japanese National Institute of Informatics) (1986-2009), Medical Online (1947-2009), and JST China (1981-2009) databases were searched for studies that compared the efficacy of hANP and the mortality in patients with acute heart failure with placebo controls. Only randomized controlled trials (RCTs) were included in the study. RESULTS Out of 347 articles, a total of 4 studies involving 220 patients with acute heart failure fulfilled the predefined inclusion criteria. There were significant differences in the hemodynamic parameters between the hANP and placebo groups, especially in the pulmonary capillary wedge pressure (PCWP) reduction (standard mean difference [SMD] 2.07; 95% confidence interval [CI], 0.34-3.81) and the cardiac index (SMD 1.79; 95% CI, 0.12-3.47). No statistically significant differences in mortality rates were found (relative risk 1.03; 95% CI, 0.27-3.92). CONCLUSIONS In a limited number of studies, hANP appears to improve several hemodynamic parameters, including pulmonary capillary wedge pressure and cardiac index, but not mortality. Further high-quality studies are needed to corroborate these results.
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6.
[The clinical value of determination of natriuretic peptides in acute coronary syndrome].
Shreĭder, EV, Shakhnovich, RM, Ruda, MIa
Terapevticheskii arkhiv. 2010;(9):63-8
Abstract
The production and release of natriuretic peptides (NPs) into the bloodstream are stimulated by increased left ventricular wall tension during volume overload. In ischemia, NPs are secreted by myocardial cells in response to stress or overload, particularly in the development of myocardial systolic dysfunction. The review details the time course of changes in amino acid N-terminal proBNP in acute coronary syndrome (ACS) with and without ST-segment elevation and discusses the role of the index in defining the tactics of treatment and prognosis in patients with ACS.
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7.
Urodilatin: a better natriuretic peptide?
Vesely, DL
Current heart failure reports. 2007;(3):147-52
Abstract
The kidney natriuretic peptide urodilatin (ie, ularitide) decreases pulmonary capillary wedge pressure (PCWP) but does not cause diuresis in persons with congestive heart failure (CHF). Thirty-three percent of patients with CHF treated with 30 ng/kg/min ularitide develop hypotension with systolic blood pressures below 90 mmHg. Nesiritide and atrial natriuretic peptide lower PCWP and cause hypotension. They do not produce diuresis or natriuresis in patients with CHF. The best natriuretic peptide for treating CHF is the cardiac hormone vessel dilator which decreases PCWP and decreases systemic and pulmonary vascular resistance while simultaneously increasing cardiac output and cardiac index. What makes the vessel dilator markedly better than atrial natriuretic peptide, nesiritide, and ularitide for treatment of CHF is that it enhances sodium excretion fivefold and causes a fivefold enhanced diuresis in patients with CHF with its biologic effects lasting over 6 hours compared with less than 30 minutes for the above peptides.
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8.
[The role of natriuretic peptides in heart failure].
Ancona, R, Limongelli, G, Pacileo, G, Miele, T, Rea, A, Roselli, T, Masarone, D, Messina, S, Palmieri, R, Golia, E, et al
Minerva medica. 2007;(5):591-602
Abstract
Over the last decades, there has been a significant increase in incidence and prevalence of heart failure, a major cause of cardiac morbidity and mortality. Measurements of neurohormones, in particular B-type natriuretic peptide (BNP), can significantly improve diagnostic accuracy, and also correlate with long-term morbidity and mortality in patients with chronic heart failure presenting to the emergency department. BNP is secreted by cardiac ventricles mainly in response to wall stress and neurohormonal factors like the sympathetic nervous system, endothelins, and the rennin-angiotensin-aldosterone system. BNP increases myocardial relaxation and oppose the vasoconstrictive, sodium retaining, and natriuretic effects caused by vasoconstrictive factors. BNP is the first biomarker to prove its clinical value for the diagnosis of left ventricular systolic and diastolic dysfunction but also for the right ventricular dysfunction, guiding prognosis and therapy management. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.
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9.
ANP and urodilatin: who is who in the kidney.
Hirsch, JR, Meyer, M, Forssmann, WG
European journal of medical research. 2006;(10):447-54
Abstract
Mounting evidence suggests that urodilatin, not atrial natriuretic peptide (ANP) is the responsible peptide in regulation of renal Na superset+- and water homeostasis. Following the discovery of ANP this peptide was thought to be responsible for the induction of natriuresis and diuresis in the mammalian kidney. However, the isolation of urodilatin from human urine and substantial work contributed to a better understanding of the renal physiology of these two natriuretic peptides. Indeed, subsequent elucidation supported that urodilatin rather than ANP seems to be the natriuretic peptide responsible for the regulation of Na superset+- and water homeostasis in the kidney. Urodilatin - synthesized and secreted from the distal tubules of the kidney - may act as a paracrine mediator when secreted into the lumen. In contrast, while the role of ANP as regulator of the cardiovascular system is established, its physiological regulatory role on transport processes in the nephron is questionable. This review attempts to analyze the roles of both ANP and urodilatin and to discuss new potential candidates which may also play a role in electrolyte and water handling in the kidney.
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10.
Serum biomarkers for heart failure.
Jarolim, P
Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. 2006;(3):144-9
Abstract
The incidence of heart failure has been steadily increasing over the past several decades. High readmission rates in patients with acute decompensated heart failure led to the search for biomarkers that could predict future clinical course and would, in an ideal case, enable monitoring of patients with heart failure and guidance of their therapy. From among several promising markers, the B-type natriuretic peptide and the biologically inactive N-terminal portion of its pro-hormone, NT-proBNP, have become the most frequently used analytes. Other known markers, such as atrial natriuretic peptide and endothelin-1, are currently used for research purposes. The development of additional biomarkers will be an important step from improving diagnosis and treatment of patients with chronic and acute decompensated heart failure.