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Nonhuman primates are commonly used as experimental animals due to their biological resemblance to humans. In patients with cardiac disease, the levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) tend to increase in response to cardiac damage, and they are thus used as indicators for the diagnosis of human heart failure. However, no reference values for ANP and BNP have been reported for heart disease in nonhuman primates. In this study, we recorded the age, sex, and body weight of 202 cynomolgus monkeys, and performed evaluations to assess the ANP and BNP levels, electrocardiography and echocardiography, and accordingly divided the monkeys into two groups: healthy monkeys and those with spontaneous cardiac disease. Statistical analysis was performed to determine the relationship of ANP and BNP with the factors of age, sex, and body weight. No significant relationship was found between the levels of ANP and BNP and the factors of age, sex, and body weight. However, both the ANP and BNP levels were significantly different between the healthy monkeys and monkeys with valvular disease. Similar to humans, the ANP and BNP levels tended to increase with the progression of cardiac disease in monkeys. Based on these results, we concluded that ANP and BNP are indicators of cardiac disease in nonhuman primates, and that this nonhuman primate cardiac disease model is applicable for cardiology research in humans.

Doxorubicin is a widely used anticancer drug that causes dose-related cardiotoxicity. The exact mechanisms of doxorubicin toxicity are still unclear, partly because most in vitro studies have evaluated the effects of short-term high-dose doxorubicin treatments. Here, we developed an in vitro model of long-term low-dose administration of doxorubicin utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Moreover, given that current strategies for prevention and management of doxorubicin-induced cardiotoxicity fail to prevent cancer patients developing heart failure, we also investigated whether the GATA4-targeted compound 3i-1000 has cardioprotective potential against doxorubicin toxicity both in vitro and in vivo. The final doxorubicin concentration used in the chronic toxicity model in vitro was chosen based on cell viability data evaluation. Exposure to doxorubicin at the concentrations of 1–3 µM markedly reduced (60%) hiPSC-CM viability already within 48 h, while a 14-day treatment with 100 nM doxorubicin concentration induced only a modest 26% reduction in hiPCS-CM viability. Doxorubicin treatment also decreased DNA content in hiPSC-CMs. Interestingly, the compound 3i-1000 attenuated doxorubicin-induced increase in pro-B-type natriuretic peptide (proBNP) expression and caspase-3/7 activation in hiPSC-CMs. Moreover, treatment with 3i-1000 for 2 weeks (30 mg/kg/day, i.p.) inhibited doxorubicin cardiotoxicity by restoring left ventricular ejection fraction and fractional shortening in chronic in vivo rat model. In conclusion, the results demonstrate that long-term exposure of hiPSC-CMs can be utilized as an in vitro model of delayed doxorubicin-induced toxicity and provide in vitro and in vivo evidence that targeting GATA4 may be an effective strategy to counteract doxorubicin-induced cardiotoxicity. Electronic supplementary material The online version of this article (10.1007/s00204-020-02711-8) contains supplementary material, which is available to authorized users.

Atrial and B-type natriuretic peptides (ANP and BNP) are cardiac hormones secreted as compensatory measures to preserve cardiorenal homeostasis. Treating heart failure (HF) with sacubitril/valsartan increased ANP and not BNP, suggesting the ANP system may confer therapeutic benefit. Thus, the presence of an ANP deficient subgroup of HF patients possibly posing higher risk for HF severity, underscores a need to characterize both, the biologically active and inactive (NT-proANP and NT-proBNP) natriuretic peptides (NPs)(latter resistant to degradation), to highlight the extent of NP production in HF. Characterizing neprilysin (NEP) activity may also provide insights into the degree of NP degradation in HF. This study aims to both highlight the cardiac NP response in acute decompensated HF(ADHF) by measuring molecular forms of ANP and BNP together with defining circulating soluble NEP activity as to assess mechanisms impairing the NP response in HF. We recruited 47 healthy individuals with neither cardiovascular nor metabolic disease and compared ANP, BNP, NT-proANP, NT-proBNP, and NEP activity levels with 107 recruited ADHF patients. In ADHF, compared to a healthy setting, median ANP, BNP, NT-proANP, and NT-proBNP were all elevated (15.7 vs. 118.1 pg/mL , p

Brain (or B-type) natriuretic peptide (BNP) is a cardiac hormone produced in the heart and an established biochemical marker for heart failure (HF) because the level in plasma increases in proportion to disease severity. Recently, the diversity of BNP molecular forms in the peripheral circulation, which includes mature BNP (BNP1-32) and its metabolites (BNP3-32, BNP4-32, and BNP5-32), was demonstrated. Moreover, studies showed that unprocessed BNP prohormone (proBNP) is also secreted from the heart, and its secretion is increased in patients with HF. Interestingly, BNP1-32, its metabolites, and proBNP are all detected as immunoreactive BNP by the currently available BNP assay system. Current N-terminal proBNP (NT-proBNP) assay systems also can react to both NT-proBNP and proBNP. In addition, the N-terminal region of proBNP and NT-proBNP are often O-glycosylated, which may result in underestimation of total NT-proBNP level, which includes both glycosylated and non-glycosylated NT-proBNP, by the NT-proBNP assay system. More recently, we have shown that miR30-GALNT-dependent O-glycosylation in the N-terminal region of proBNP affects the processing of proBNP and contributes to its secretion from the heart. The level of proBNP relative to BNP (proBNP/BNP ratio) in the coronary sinus is higher in patients with more severe HF. The proBNP/BNP ratio and the deglycosylated NT-proBNP level may be new and clinically useful biomarkers of HF.

B-type natriuretic peptide (BNP) is a cardiac hormone widely used as a biomarker for heart failure. Here, we present the first report of extremely high levels of immunoreactive BNP caused by formation of macro-proBNP. A 70-year-old woman with left ventricular hypertrophy and normal systolic function presented with extremely high plasma levels of BNP (35,374pg/ml) and N-terminal proBNP (NT-proBNP; 30,600pg/ml). Our recently developed proBNP immunoassay showed that nearly 100% of her immunoreactive BNP was proBNP. Polyethylene glycol precipitation tests reported extremely low BNP recovery (1.3%), while protein G addition tests also reported a remarkably low BNP fraction (3.3%). Gel filtration chromatography with normal elution buffer combined with BNP immunoassays showed a BNP peak with a retention time slightly shorter than that of IgG. With acidic elution buffer (pH3.0), however this peak disappeared and a new BNP peak consistent with glycosylated human proBNP appeared. These results suggest that in this case most BNP immunoreactivity consisted of macro-proBNP, which is an immune complex composed of proBNP and an anti-proBNP autoantibody. Gel filtration chromatography combined with NT-proBNP immunoassays revealed that the NT-proBNP assay cross-reacts with both the proBNP-IgG complex and proBNP. In addition, with acidic buffer, a new large peak appeared with a retention time the same as that of glycosylated NT-proBNP. These results suggest spuriously high levels of BNP and NT-proBNP are caused by macro-proBNP. Macro-NT-proBNP is not detected by the currently available NT-proBNP assay system.

Cardiovascular disease (CVD) has a tremendous impact on the quality of life of humans. While experimental animals are valuable to medical research as models of human diseases, cardiac systems differ widely across various animal species. Thus, we examined a CVD model in cynomolgus monkeys. Laboratory primates are precious resources, making it imperative that symptoms of diseases and disorders are detected as early as possible. Thus, in this study we comprehensively examined important indicators of CVD in cynomolgus monkeys, including arterial blood gas, complete blood count (CBC), biochemistry and cardiac hormones. The control group included 20 healthy macaques showing non-abnormal findings in screening tests, whereas the CVD group included 20 macaques with valvular disease and cardiomyopathy. An increase of red blood cell distribution width was observed in the CBC, indicating chronic inflammation related to CVD. An increase of HCO3 was attributed to the correction of acidosis. Furthermore, development of the CVD model was supported by significant increases in natriuretic peptides. It is suggested that these results indicated a correlation between human CVD and the model in monkeys. Moreover, blood tests including arterial blood gas are non-invasive and can be performed more easily than other technical tests. CVD affected animals easily change their condition by anesthesia and surgical invasion. Pay attention to arterial blood gas and proper respond to their condition are important for research. This data may facilitate human research and aid in the management and veterinary care of nonhuman primates.

Cardiac natriuretic peptides have long been known to act as main players in the homeostatic control of blood pressure, salt and water balance. However, in the last few decades, new properties have been ascribed to these hormones. A systematic review of English articles using MEDLINE Search terms included prostate cancer, inflammation, cardiac hormones, atrial natriuretic peptide, and brain natriuretic peptide. Most recent publications were selected. Natriuretic peptides are strongly connected to the immune system, whose two branches, innate and adaptive, are finely tuned and organized to kill invaders and repair injured tissues. These peptides control the immune response and act as anti-inflammatory and immune-modulatory agents. In addition, in cancers, natriuretic peptides have anti-proliferative effects by molecular mechanisms based on the inhibition/regulation of several pathways promoting cell proliferation and survival. Nowadays, it is accepted that chronic inflammation is a crucial player in prostate cancer development and progression. In this review, we summarize the current knowledge on the link between prostate cancer and inflammation and the potential use of natriuretic peptides as anti-inflammatory and anticancer agents.

Circulating levels of leptin are increased in obesity and have been proposed to contribute to the development of hypertension in obese individuals. Four cardiac hormones, specifically, vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide and atrial natriuretic peptide (ANP), have blood pressure-lowering properties and correlate with the presence of hypertension in obesity. The objective of this study was to determine whether one or more of these cardiac hormones was able to decrease the levels of leptin in the hypothalamus, an area of the brain that has been demonstrated to synthesize more than 40% of leptin in the circulation. The effects of these four cardiac hormones on leptin were examined using dose-response curves in the rat hypothalamus, which synthesizes leptin. Vessel dilator, LANP, kaliuretic peptide and ANP maximally decreased the levels of leptin in hypothalamic cells by 79, 76, 80 and 62%, respectively (P

Background: serum level of amino-terminal pro-B-type natriuretic peptide, a cardiac hormone produced by the heart, is elevated in patients with left ventricular dysfunction. The purpose of this study was to compare the abilities of serum and pericardial fluid levels of amino-terminal pro-B-type natriuretic peptide to detect the left ventricular systolic dysfunction determined by echocardiography. Methods: 50 patients undergoing coronary artery bypass grafting were included in this study. Left ventricular systolic function was assessed using echocardiography before coronary artery bypass grafting. The samples of serum and pericardial fluid were collected during surgery, and amino-terminal pro-B-type natriuretic peptide levels were assessed by an electrochemiluminescence immunoassay. The log value of amino-terminal pro-B-type natriuretic peptide concentrations was calculated. Results: the pericardial fluid levels of log amino-terminal pro-B-type natriuretic peptide were significantly elevated compared to the serum levels in patients with impaired left ventricular systolic function. Both serum and pericardial fluid levels of log amino-terminal pro-B-type natriuretic peptide correlated significantly with left ventricular ejection fraction and end-diastolic and end-systolic volume indices. Furthermore, a paired comparison of receiver operating characteristic curves showed a similar performance of amino-terminal pro-B-type natriuretic peptide levels both in serum and pericardial fluid to discriminate left ventricular systolic dysfunction. Conclusion: serum amino-terminal pro-B-type natriuretic peptide levels have comparable diagnostic value for left ventricular systolic dysfunction with its pericardial fluid levels in patients undergoing CABG.

Techniques developed over the years in our laboratory for the study of tissue expression, storage, and secretion of the cardiac hormones ANF, BNP, and CNP are described below. They have proven highly reliable in our hands when the steps outlined are followed as described. Given the generic nature of the procedures, these should be applicable to other polypeptides.

Accurately defining haemodynamically significant patent ductus arteriosus (PDA) in preterm infants who are at risk of PDA related morbidities are active areas of neonatal research. Natriuretic peptides are cardiac hormones that respond to volume and pressure loading, with elevated plasma levels found in infants with PDA. In the preterm neonatal setting, studies to date have predominantly investigated the ability of these biomarkers to discriminate between infants with and without a PDA at various postnatal ages. Their clinical utility has therefore been exclusively evaluated as a method of triaging cases of suspected hsPDA to decrease the need for echocardiograms, and to monitor treatment response. Biomarkers are yet to be robustly investigated for their ability to predict important PDA associated morbidities. In this review, we examine the most recent literature to date on the use of biomarkers in the management of PDA.

Natriuretic peptides (NPs) are traditionally known as cardiac hormones with diuretic, natriuretic and blood pressure lowering properties. Evidence indicates that NPs and their receptors are abundant in the central nervous system, suggesting their involvement in regulation of various brain functions. It has been shown that NPs are involved in the regulation of neurovascular and blood-brain barrier integrity, neuro-inflammation, neuroprotection, synaptic transmission and brain fluid homeostasis. In addition, NPs might contribute to the brain's inhibitory control over the hypothalamic-pituitary-adrenal axis. Studies have also shown that high systemic levels of NPs are associated with cognitive impairment independent of cardiovascular risk factors. In this review we discuss the potential roles of NPs in regulating structural and functional integrity of the brain. Based on the available neurobiological and clinical evidence, we propose that NPs might represent as potential novel diagnostic and therapeutic targets for cognitive impairment.

Brain natriuretic peptide (BNP) is well known cardiac hormone released from the left ventricle myocardium as result of heart wall injury. It is a often used biochemical marker of heart failure. Its greatest role is in distinguishing etiology of dyspnea. The role of BNP in cirrhotic patients is not fully explored jet. It is well known that cirrhosis leads to diastolic and consequently systolic dysfunction, causing increase of BNP values. BNP could be a good follow up marker in cirrhotic patients, and a marker od liver decompensation, since its values positively correlate with Child Pough score, and other complications of liver cirrhosis. There are more studies needed in this field.

Secreted frizzled-related proteins (sFRPs) are secreted glycoproteins involved in neoplastic growth. Four hormones synthesized in the heart, namely vessel dilator, atrial natriuretic peptide (ANP), kaliuretic peptide (KP) and long-acting natriuretic peptide (LANP), have anticancer effects both in vitro and in vivo. These heart hormones were evaluated for their ability to inhibit sFRP-3, which is associated with tumor invasiveness, in human pancreatic cancer, colorectal cancer and renal adenocarcinoma cell lines. Vessel dilator, KP, ANP and LANP maximally reduced the concentration of sFRP-3 by 83%, 83%, 84% and 83%, respectively (each at P

Natriuretic peptides (NPs) are hormones which are mainly secreted from heart and have important natriuretic and kaliuretic properties. There are four different groups NPs identified till date [atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and dendroaspis natriuretic peptide, a D-type natriuretic peptide (DNP)], each with its own characteristic functions. The N-terminal part of the prohormone of BNP, NT-proBNP, is secreted alongside BNP and has been documented to have important diagnostic value in heart failure. NPs or their fragments have been subjected to scientific observation for their diagnostic value and this has yielded important epidemiological data for interpretation. However, little progress has been made in harnessing the therapeutic potential of these cardiac hormones.

Atrial natriuretic peptide (ANP), a new cardiac hormone, has potent natriuretic, diuretic and vaso-relaxant properties in animals and humans. Plasma ANP levels increased in response to volume expansion, atrial distension or postural change. The present investigation was designed to examine the effect of labour on plasma ANP in normotensive pregnant women. The results show that plasma ANP in pregnant women (n = 9) increased significantly in active phase of first stage of labour from 19.5 +/- 4.6 pg/ml to 74.5 +/- 15.1 pg/ml. The magnitude of the increase in ANP levels in active phase varied among the patients. During and after delivery, plasma ANP decreased in all instances towards control level. The cause for the increase in plasma ANP levels in the active phase remains to be determined.

Since the discovery of B-type natriuretic peptide (BNP) as a cardiac hormone in 1991, it has been well studied as a diagnostic and prognostic marker in heart failure (HF). BNP has also been investigated for its role in cost-effectiveness, as a guide to therapy, as a therapy itself, as inclusion

In 1956, secretory granules were detected via electron microscopy in the mammalian atria by Kisch. This remarkable discovery signaled the beginning of a new field of research that decades later has lead to the concept of the heart as an endocrine organ and the establishment of the natriuretic peptide (NP) system. In 1981, deBold and colleagues identified from the atrial myocardium the first member of the NP family, atrial NP. Thereafter, new members of this growing family of cardiac hormones were identified and investigated. The successful story of B-type or brain NP (BNP), from its discovery to its use in the diagnosis and prognosis of cardiovascular diseases and later as a tool in the treatment of acute congestive heart failure, have since taken place. However, the use of peptides as chronic therapies has been limited by enzymatic degradation. Chronic administration of BNP, particularly in disease states like hypertension and early heart failure, could be effective as an antihypertensive therapy and in delaying progression of cardiac disease. To date, the use of BNP is limited to patients with acute decompensated heart failure, but new strategies are under investigation to extend the use of chronic BNP in less severe stages of cardiovascular diseases. Innovative technologies have been recently developed that allow protection of proteins from enzymatic degradation, making feasible oral administration of small proteins such as BNP. This review will focus on the potential role of BNP as a new chronic therapeutic strategy in the treatment of cardiovascular diseases and will summarize our recent report of the development and in vivo evaluation of orally active human BNP.

Background: The natriuretic peptides are a family of structurally similar peptides. Atrial natriuretic peptide and B-type natriuretic peptide (BNP) are cardiac hormones secreted from the heart in response to cardiac chamber distention. Their biological actions include diuresis, natriuresis and vasodilatation, as well as suppression of the renin-angiotensin-aldosterone and endothelin systems. The hemodynamic actions of the secreted natriuretic peptide unload the heart in response to increased intravascular volume. Knowledge regarding the biological actions of the natriuretic peptides continues to evolve into clinical use. A synthetic BNP analogue has shown a beneficial short-term effect in acute decompensated heart failure, while plasma levels of natriuretic peptides have been shown to be elevated in patients with heart disease. Conclusions: BNP and the N-terminal segment of its prohormone, NT-pro-BNP, are very sensitive markers for many forms of heart disease. Future research will likely allow greater use of these peptides in the diagnosis and treatment of heart diseases in adults and children.

Introduction Natriuretic peptides, including N-terminal-proatrial natriuretic peptide (NT-proANP) are cardiac hormones that are produced in response to myocardial stretch and have been used in rats and humans as blood based functional cardiac biomarkers. There are limited validation data of these assays in rats and therefore the Predictive Safety Testing Consortium, Cardiac Hypertrophy Working Group (PSTC—CHWG) performed a cross-laboratory (5 laboratories) analytical evaluation of a commercially available NT-proANP ELISA for use with rat samples. Methods Serum samples were collected from normal Sprague Dawley (SD) rats and were spiked with kit calibrator material or rat heart tissue extracts to provide specimens for the validation. In addition, the cardiotoxicant, isoproterenol, was used to induce elevated endogenous NT-proANP levels in a subgroup of rats for additional validation specimens. The Biomedica™ (BI-20892, Vienna, Austria) proANP (1-98) enzyme-linked immunoabsorbent assay (ELISA) kit was used to measure NT-proANP. Intra-assay and inter-assay precisions, accuracy, sample linearity, recovery, limit of detection, upper and lower limits of quantitation (ULOQ and LLOQ, respectively), sample-freeze/thaw stability and stored sample stability were assessed and compared to pre-determined acceptance criteria. Results The majority of the experimental assessments met the established validation criteria, however there were individual results that did not meet these standards. Overall, acceptable intra- and inter-assay precisions and accuracies as well as inter-laboratory precision and accuracy were demonstrated. Linearity and recovery values fell within the pre-determined acceptance criteria, samples remained stable for up to three freeze–thaw cycles and frozen samples were stable at ~− 70 °C for 12 months. The limit of detection (LOD) and LLOQ and ULOQ were similar to those specified by the manufacturer. Discussion Overall, the assay was demonstrated to be technically adequate for the detection of NT-proANP serum levels in SD rats.

Background: Since the discovery of cardiac hormones almost 25 years ago, a vast amount of clinical research has identified the cardiac natriuretic peptides and their precursors as markers of heart failure. It even seems likely that the pro-B-type natriuretic peptide (proBNP)-derived peptides in plasma may become the most frequently measured peptides in the daily diagnosis and control of therapy. In contrast, the biochemistry of the peptides has received less attention.Methods: Published data available on the National Library of Medicine (NLM) were used as the basis for the review.Outcome: This review shows that the present understanding of the biochemistry of peptides is far from complete. In particular, cellular synthesis, including posttranslational precursor maturation, is poorly understood. Moreover, elimination of the precursor fragments is unknown. Elucidation of the molecular heterogeneity of proBNP products will therefore contribute to the understanding of the endocrine heart and may also have important diagnostic consequences. Above all, the different proBNP-derived peptides may not always be equal markers of the same pathophysiologic processes. A different metabolism and peripheral elimination may also impose new and peptide-specific limitations for diagnostic use.Conclusions: It is necessary to focus more on the biology of the proBNP-derived peptides. In turn, new insight into the biochemistry could pave the way for more sensitive and disease-specific assays in the clinical setting.

Objective Plasma atrial and brain natriuretic peptide (ANP and BNP) are cardiac hormones secreted mainly due to cardiac overload. The study was designed to assess plasma concentrations of ANP and BNP in patients undergoing coronary bypass grafting (CABG) with long and short duration of cardiopulmonary bypass (CPB) and without CPB (off-pump surgery). Methods We studied 45 patients scheduled for elective CABG. Patients were allocated in three groups: group A received CPB with a duration less than 60 minutes, group B more than 60 minutes and patients without CPB were allocated in group C. ANP and BNP were measured after induction of anaesthesia (T0), at the end of surgery (T1), 4 hrs. (T2), 24 hrs. (T3) and 120 hrs. postoperatively (T4). Results In all groups, ANP-levels increased from T0 to T4 (group A: from 3.7 +/- 2.1 to 8.9 +/- 8.0; group B: from 3.3 +/- 1.7 to 8.0 +/- 6.0; group C: from 3.0 +/- 1.6 to 5.3 +/- 2.3 pg/ml), but there were no significant differences between the groups. BNP-concentrations increased also from T0 to T4 (group A: from 34 +/- 18 to 234 +/- 164; group B: from 33 +/- 26 to 219 +/- 182; group C: from 33 +/- 24 to 77 +/- 55 pg/ml). Furthermore we measured significant higher BNP-levels in group B compared to group C at T3 and T4. No significant differences between group A and B were found. Conclusions CPB influenced BNP, but not ANP plasma concentrations. An influence of the duration of CPB on ANP and BNP was not seen.

Summary Vessel dilator, a hormone synthesized in the heart, eliminates 71% of human small-cell lung cancers and 67% of human breast cancers growing in mice when given subcutaneously (s.c.) via osmotic pumps. The pharmacokinetics of s.c. administered vessel dilator have not been evaluated previously. In the present study, the pharmacokinetics of vessel dilator following s.c. bolus (ScB) or 3 h s.c. infusion (ScI) were compared with those following i.v. bolus (IvB) administration in male Fischer 344 rats. The half-life (t½) of vessel dilator after ScI, IvB and ScB was 54, 43 and 30 min, respectively. The tmax for vessel dilator after IvB, ScB and ScI administration was 1.5, 23 and 156 min, respectively, whereas the corresponding Cmax values were 3749, 887 and 471 ng/L (normalized against the dose used for ScB and IvB). The area under the curve (AUC0–∞) for vessel dilator was 1166, 880 and 1652 ng h/mL (normalized) following IvB, ScB and ScI administration, respectively. The volume of distribution for vessel dilator was 2.38, 0.92 and 1.08 L following IvB, ScB and SCI administration, respectively; corresponding clearance values were 1.69, 1.50 and 0.78 L/h, respectively. Plasma concentrations of vessel dilator after each of the three methods of administration mirrored their predicted concentration–time profiles. We conclude that vessel dilator administered via ScI has a significantly greater AUC and t½ and slowed clearance compared with IvB or ScB administration (P

Atrial natriuretic peptide (ANP) is a cardiac hormone playing a crucial role in cardiovascular homeostasis mainly through blood volume and pressure regulation. In the last years, the new property ascribed to ANP of inhibiting tumor growth both in vitro and in vivo has made this peptide an attractive candidate for anticancer therapy. The molecular mechanism underlying the anti-proliferative effect of ANP has been mainly related to its interaction with the specific receptors NPRs, through which this natriuretic hormone inhibits some metabolic targets critical for cancer development, including the Ras-MEK1/2-ERK1/2 kinase cascade, functioning as a multikinase inhibitor. In this review we summarize the current knowledge on this topic, focusing on our recent data demonstrating that the antitumor activity of this natriuretic hormone is also mediated by a concomitant effect on the Wnt/?-catenin pathway and on the pH regulation ability of cancer cells, through a Frizzled-related mechanism. This peculiarity of simultaneously targeting two processes crucial for neoplastic transformation and solid tumor survival reinforces the utility of ANP for the development of both preventive and therapeutic strategies

Heart failure is a major global health problem affecting 23 million people worldwide. As more cardiac patients survive and live longer with this progressive disease, heart failure is a condition for which the prevalence will grow. Based solely on clinical presentation, heart failure can be difficult to diagnose since its presentation is complex, with signs and symptoms that are nonspecific and may not always be present. B-type natriuretic peptide (BNP)7 and N-terminal proBNP (NT-proBNP) are well established, clinically validated biomarkers that have been shown to improve the diagnostic accuracy for heart failure and provide prognostic information for risk stratification. The widespread clinical use of these biomarkers for more than a decade is reflected by their incorporation into national and international medical guidelines for heart failure, at the highest classification for recommendation. BNP is a cardiac hormone secreted by cardiomyocytes into the circulation in response to states of volume expansion and pressure overload, as is the case in heart failure. BNP's diuretic, natriuretic, and vasodilatory actions, and its protective effects on endothelial function and vascular remodeling, act to relieve the adverse consequences of heart failure. During the synthesis and processing of BNP, its 108 amino acid biologically inactive precursor, proBNP, is proteolytically cleaved to form the 32 amino acid peptide BNP and the 76 amino acid peptide NT-proBNP. While BNP is physiologically active, NT-proBNP is biologically inert. Due to its secretion at a 1:1 ratio to BNP and its longer half-life (90–120 min vs 20 min for BNP), the measurement of NT-proBNP has proven to have an essentially equivalent clinical performance to BNP as a biomarker for heart failure. In recent years, the simplistic model for the processing of BNPs has undergone a dramatic shift, with a better understanding of the complexity of their posttranslational modification and secretion. ProBNP is …

The cardiac hormone atrial natriuretic factor (ANF or ANP) plays significant, well-established roles in a large number of physiological and pathophysiological processes, including water and electrolyte balance, blood pressure regulation, and cardiovascular growth. Understanding the regulation of its production and secretion by atrial cardiomyocytes is incomplete. We have previously established a significant role of Gi/oprotein signaling in modulating ANF secretion as promoted by stretch of the atrial myocardium. In the present study, we investigated the role of Gqprotein signaling and its relationship to Gi/oprotein signaling using pharmacological manipulation of proximal effectors of Gαqin an ex vivo model of spontaneously beating rat atria. Phospholipase C (PLC) and protein kinase C (PKC) inhibitors dramatically increased basal secretion of ANF. Furthermore, although atrial wall stretch is a potent stimulus for secretion, stretch unexpectedly reduced ANF secretion to basal levels under PLC and PKC inhibitory conditions. Inhibition of the inositol triphosphate receptor did not appear to affect basal secretion but dose-dependently blocked stretch-secretion coupling. The results obtained demonstrate that the PLC and PKC signaling cascades play important albeit unexpected roles in the regulation of basal and stimulated ANF secretion and suggest interplay between the Gqand Gi/oprotein signaling pathways.

Heart failure is currently the number one killer and most expensive single diagnosis in developed countries. Despite improved treatment over the past few decades, more people are living with heart failure, leading to an increase in the overall incidence. Clearly, more effective treatments are needed. What if we learned that a treatable, cardiac hormone deficiency that is known to actually cause heart failure may be present in most cardiac patients but largely going undetected and/or ignored? What if correction of this hormone deficiency could be done safely, improve coronary blood flow and contractile function, reverse neurohormonal activation, and also reverse most of the abnormally functioning cardiac genes associated with heart failure? Certainly, any newly developed, patentable drug accomplishing this feat would receive considerable attention. But alas, I am referring to generic thyroid hormones, something that would save, rather than incur billions in global health costs if proven effective. Yes, thyroid hormone treatment of heart disease has been suggested before and the medical community is flatly opposed, believing the issue was settled long ago. But, if one takes a fair and objective look at the older literature that largely shaped the current opinion, the conclusion should be that “toxic” doses of thyroid hormones can lead to increased arrhythmias and mortality. The issue of long-term use of “therapeutic” doses of thyroid hormones in chronic heart failure has never been adequately studied, despite positive results from many short-term studies. More recent information also provides important mechanistic insight and begs re-examination of the topic [1]

The presence of natriuretic and vasorelaxant materials in the atria and ventricles of a Chelonian reptile, the freshwater turtle Pseudemys scripta, was verified and the active substance partially characterized. Crude atrial and ventricular extracts were acutely natriuretic and diuretic when administered to anesthetized rats increasing sodium excretion 23.5 +/- 7.9 and 5.11 +/- 18 microM Na/10 min/mg extract, respectively. Although atrial extracts were relatively more natriuretic than ventricular extracts, the total natriuretic content of ventricular extracts was approximately twofold greater. Moreover, partially purified atrial extracts were found to relax precontracted isolated rat aortic ring segments and exhibited immunoreactivity to mammalian ANP antisera. Also, the natriuretic and immunoreactive substance was purified further by size exclusion chromatography and a molecular weight of 3-5 kDa was determined. Using the bovine adrenal glomerulosa ANP receptor, this partially purified natriuretic substance displayed an apparent binding affinity similar to that of mammalian ANP. Finally, in order to demonstrate that this reptile is physiologically responsive to ANP, synthetic rat ANP (10 micrograms/kg) was shown to decrease arterial pressure in conscious turtles from a control value of 37.2 +/- 5.2 to 30.3 +/- 2.7 mm Hg. These data demonstrate that unlike other non-Chelonian reptiles, both the atria and the ventricles of this Chelonian reptile synthesize and store substantial levels of biologically active ANP-like materials, and further, that ANP is a highly conserved and primitive cardiac hormone.

This article provides a brief overview of atrial natriuretic factor (ANF). Considered by many investigators to be the putative "third factor" governing sodium excretion, ANF is a peptide actively secreted by the heart, with multiple target organ effectors. As such, ANF represents the first clearly documented cardiac hormone.

Since the discovery of the cardiac hormone atrial natriuretic peptide (ANP) by DeBold and coworkers in 1981 [1], the field of natriuretic peptides has advanced significantly, with translation of new knowledge to the clinical practice of heart failure (HF). This new knowledge has underscored the importance of cardiorenal mechanisms that contribute to optimal cardiovascular homeostasis. Work has also established direct myocardial actions broadening their therapeutic potential beyond renal mechanisms. Indeed, one such therapeutic target is cardiac remodeling and fibrosis based upon the unique cardiorenal protective properties. The objective of this article is to review new insights into the use of natriuretic peptides as novel therapeutic agents for cardiorenal protection in progressive HF, which serves to limit cardiac remodeling and fibrosis and thus the progression of HF.

Background B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are small cardiac hormones released from the heart. They can be used as an important aid to diagnose congestive heart failure (CHF). Methods We compared the performances of the Abbott AxSYM and Roche Elecsys 2010 for the measurement of BNP and NT-proBNP. The first method uses a microparticle enzyme-linked immunoassay, whereas the other uses chemiluminescent immunometric assay. Results The CVs using pooled sera ranged from 3.7% to 12.7% for the AxSYM and 0.9% to 2.2% for the Elecsys 2010. The Passing and Bablok regression was Elecsys 2010 NT-proBNP = 7.23 × AxSYM BNP + 2.53. The BNP in EDTA plasma was more stable than in serum. The immunoreactivity difference of NT-proBNP in serum or EDTA plasma was within 10% when stored at 4 °C or 25 °C for 72 h. Receiver operating characteristic (ROC) curves were different for both assays, and the areas under the curves were 0.704 and 0.841 for the AxSYM and Elecsys 2010 method, respectively. Conclusions Both assays were not entirely specific for heart failure. The precision and stability for NT-proBNP was better than for BNP in serum. It is important to use method-appropriate reference ranges (or cutoff) for the BNP and NT-proBNP, respectively, in the assessment of CHF.