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High adiponectin concentrations are generally regarded as beneficial with regard to cardiometabolic health, but have been paradoxically associated with increased cardiovascular disease risk, specifically heart failure, in individuals at high cardiovascular risk. We aimed to investigate the association between adiponectin and heart function parameters, and inversely, we estimated the effect of genetically-determined heart function and NT-proBNP as the main marker of heart failure on adiponectin using Mendelian randomisation. Observational analyses between adiponectin and measures of heart function, i.e. E/A ratio, left, and right ventricular ejection fraction, were performed in participants of the Netherlands Epidemiology of Obesity (NEO) study, assessed by MRI of the heart (n = 1,138). Two-sample Mendelian randomisation analyses were conducted to estimate the effect of NT-proBNP and heart function on adiponectin concentrations using publicly-available summary statistics (ADIPOGen; the PLATO trial). The mean (standard deviation) age was 56 (6) years and mean body mass index was 26 (4) kg/m 2 . Per five μg/mL higher adiponectin, the E/A ratio was -0.05 (95 % CI: -0.10, -0.01) lower, left ventricle ejection fraction was -0.5 % (95 % CI: -1.1, 0.1) lower, and right ventricle ejection fraction was 0.5 % (95 % CI: -0.1, 1.2) higher. Genetically-determined NT-proBNP was causally related to adiponectin concentrations in ADIPOGen: per doubling of genetically-determined NT-proBNP, adiponectin concentrations were 11.4 % (95 % CI: 1.7, 21.6) higher. With causal MR methods we showed that NT-proBNP affects adiponectin concentrations, while adiponectin is not associated with heart function parameters. Therefore, reverse causation may explain the adiponectin paradox observed in previous studies., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Periostin, an extracellular matrix and matricellular protein, binds to several types of integrins that transduce its signals. Its function in allergic inflammation is the establishment of sustained chronic inflammation through an amplification of T helper type 2‒immune responses. In addition, recent studies have shown a significant role of periostin in itch sensation through direct integrin-mediated stimulation of nerve fibers and interaction with immune and nonimmune cells (e.g., macrophages, eosinophils, basophils, and keratinocytes). The objective of this review is to describe the role of periostin in itch induction in human and animal models and its expression in human pruritic conditions., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

As the heart matures during embryogenesis from its foetal stages, several structural and functional modifications take place to form the adult heart. This process of maturation is in large part due to an increased volume and work load of the heart to maintain proper circulation throughout the growing body. In recent years, it has been observed that these changes are reversed to some extent as a result of cardiac disease. The process by which this occurs has been characterized as cardiac foetal reprogramming and is defined as the suppression of adult and re-activation of a foetal genes profile in the diseased myocardium. The reasons as to why this process occurs in the diseased myocardium are unknown; however, it has been suggested to be an adaptive process to counteract deleterious events taking place during cardiac remodelling. Although still in its infancy, several studies have demonstrated that targeting foetal reprogramming in heart failure can lead to substantial improvement in cardiac functionality. This is highlighted by a recent study which found that by modulating the expression of 5-oxoprolinase (OPLAH, a novel cardiac foetal gene), cardiac function can be significantly improved in mice exposed to cardiac injury. Additionally, the utilization of angiotensin receptor neprilysin inhibitors (ARNI) has demonstrated clear benefits, providing important clinical proof that drugs that increase natriuretic peptide levels (part of the foetal gene programme) indeed improve heart failure outcomes. In this review, we will highlight the most important aspects of cardiac foetal reprogramming and will discuss whether this process is a cause or consequence of heart failure. Based on this, we will also explain how a deeper understanding of this process may result in the development of novel therapeutic strategies in heart failure., (© 2020 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Investigations into the mixed muscle-secretory phenotype of cardiomyocytes from the atrial appendages of the heart led to the discovery that these cells produce, in a regulated manner, two polypeptide hormones - the natriuretic peptides - referred to as atrial natriuretic factor or atrial natriuretic peptide (ANP) and brain or B-type natriuretic peptide (BNP), thereby demonstrating an endocrine function for the heart. Studies on the gene encoding ANP (NPPA) initiated the field of modern research into gene regulation in the cardiovascular system. Additionally, ANP and BNP were found to be the natural ligands for cell membrane-bound guanylyl cyclase receptors that mediate the effects of natriuretic peptides through the generation of intracellular cGMP, which interacts with specific enzymes and ion channels. Natriuretic peptides have many physiological actions and participate in numerous pathophysiological processes. Important clinical entities associated with natriuretic peptide research include heart failure, obesity and systemic hypertension. Plasma levels of natriuretic peptides have proven to be powerful diagnostic and prognostic biomarkers of heart disease. Development of pharmacological agents that are based on natriuretic peptides is an area of active research, with vast potential benefits for the treatment of cardiovascular disease.

Natriuretic peptides (NP), especially B type (BNP) and its N-terminal pro-B type natriuretic peptide (NT-proBNP), have long been regarded as biomarkers of volume overload and tools to exclude heart failure in the general population. However, their role in end-stage kidney disease (ESKD) is less certain given that BNP and NT-proBNP are excreted by the kidney and so serum concentrations of NPs are nearly universally elevated compared to controls. Nevertheless, the accumulated evidence suggests thatserum concentrations of NPs in patients with ESKD show moderate or strong positive relationships with underlying heart disease, abnormal cardiac structure or function and mortality. Limited evidence also supports the role of BNP including NT-proBNP, ANP in some studies, rather than CNP or DNP in risk stratification among ESKD patients as well as the utility of BNP samplings pre- and post- hemodialysis. However, studies of the cut-off values of NPs have yielded inconsistent results, such that further large-scale studies are needed to clarify these issues. This review summarizes the pathophysiology and significance of NPs in ESKD patients, especially their potential role as risk stratification biomarkers in clinical management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Sepsis continues to be a leading public health burden in the United States and worldwide. With the increasing use of advanced laboratory technology, there is a renewed interest in the use of biomarkers in sepsis to aid in more precise and targeted decision-making. Natriuretic peptides have been increasingly recognized to play a role outside of heart failure. They are commonly elevated among critically ill patients in the setting of cardiopulmonary dysfunction and may play a role in identifying patients with sepsis and septic shock. There are limited data on the role of these biomarkers in the diagnosis, management, outcomes and prognosis of septic patients. This review seeks to describe the role of natriuretic peptides in fluid resuscitation, diagnosis of ventricular dysfunction and outcomes and the prognosis of patients with sepsis. B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) have been noted to be associated with left ventricular systolic and diastolic and right ventricular dysfunction in patients with septic cardiomyopathy. BNP/NT-proBNP may predict fluid responsiveness, and trends of these peptides may play a role in fluid resuscitation. Despite suggestions of a correlation with mortality, the role of BNP in mortality outcomes and prognosis during sepsis needs further evaluation.

B-type natriuretic peptide (BNP) was approved by the US Food and Drug Administration in 2001 for the treatment of heart failure. However, the effects of BNP in clinical applications are controversial and uncertain. Recently, study indicated that high BNP levels are associated with an increased risk of developing atrial fibrillation. In this study, we investigated the direct effects of BNP on TNF-α-induced atrial fibrosis mice, as well as its effects on human atrial myofibroblasts. We found that injecting TNF-α-induced mice with recombinant human BNP enhanced atrial fibrosis via matrix metalloproteinase-2 (MMP-2) expression and collagen accumulation. Furthermore, we found that BNP stimulated MMP-2 expression in human atrial myofibroblasts. Treatment of human atrial myofibroblasts with cycloheximide had no effect on this outcome; however, treatment of cells with MG132 enhanced BNP-induced MMP-2 expression, indicating that protein stability and inhibition of proteasome-mediated protein degradation pathways are potentially involved. Inhibition of SIRT1 significantly decreased BNP-induced MMP-2 expression. Additionally, confocal and coimmunoprecipitation data indicated that BNP-regulated MMP-2 expression are likely to be mediated through direct interaction with SIRT1, which is thought to deacetylate MMP-2 and to increase its protein stability in human atrial myofibroblasts. Finally, we confirmed that SIRT1 is expressed and cytoplasmically redistributed as well as colocalized with MMP-2 in mouse fibrotic atrial tissue. We suggest a possible fibrosis-promoting role of BNP in the atrium, although the antifibrotic properties of BNP in the ventricle have been reported in previous studies, and that the coordination between MMP-2 and SIRT1 in BNP-induced atrial myofibroblasts participates in atrial fibrosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diabetic nephropathy is associated with increased risk of cardiovascular disease. B-type natriuretic peptide (BNP) plays an important role in cardiovascular pathophysiology and therapeutics. The aim of the present study was to investigate the influence of experimental diabetes on the mechanisms that regulate the relaxant response of the rabbit renal artery to BNP. Arterial relaxations to BNP were enhanced in diabetic rabbits. Indomethacin enhanced BNP-induced relaxation in control rabbits but showed no effect in diabetic rabbits. BNP-induced release of thromboxane A 2 or prostacyclin was not different in both groups of animals. Iberiotoxin had no effect on relaxations to BNP in both groups of animals. Charybdotoxin displaced to the right the concentration-response curve to BNP in both group of animals, and inhibited BNP-induced relaxation only in diabetic rabbits. Glibenclamide did not modify the BNP-induced relaxations in control rabbits, but inhibited it in diabetic rabbits. These results suggest that diabetes induces hypereactivity of the rabbit renal artery to BNP by mechanisms that at least include (1) a reduced vasoconstrictor influence of arachidonic acid metabolites via cyclooxygenase 2, which is not related with changes in thromboxane A 2 and prostacyclin release from the arterial wall and (2) a selectively increased modulatory activity of K ATP and endothelial IK Ca channels.

The primary purpose of the study was to evaluate whether a pericardiectomy (PERI) alters training- or myocardial infarction (MI)-induced left ventricular hypertrophy (LVH), chamber geometry, gene expression and/or running performance. Mice were randomized into 6 groups: naïve control (CONT)-sedentary (Sed), CONT-trained (Tr), PERI-Sed, PERI-Tr, MI-Sed and MI-Tr. MI mice also received a pericardiectomy as part of the MI surgical procedure. 10 weeks of treadmill running resulted in enhanced running performance-to-exhaustion in all 3 trained groups (CONT-Tr, PERI-Tr, MI-Tr) compared to sedentary cohorts ( P <0.001). Training also resulted in similar increases in normalized LVH (LV/BW) in CONT-Tr and PERI-Tr mice. 2D-echocardiographic evaluation of LV internal chamber dimensions revealed that stroke diameter (SD) was larger in PERI compared to MI ( P <0.01) but not CONT mice. Ventricular B-type natriuretic peptide mRNA (BNP) was elevated only in the 2 MI groups. Left ventricle β 1 -adrenergic receptor (β 1 -AR) and melusin transcripts both demonstrated an overall increase in trained compared to sedentary mice (both P <0.05). Additionally long-term pericardiectomy did not further enhance running performance or increase LV/BW in either sedentary or trained mice., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To analyze the clinical outcomes of emergency percutaneous intervention in acute myocardial infarction (AMI) during hospital, and to find the relevant risk factors for the prognosis and cardiac events. 
 Methods: We retrospective analyzed the patient with acute ST segment elevation myocardial infarction, who was successfully performed emergency percutaneous coronary intervention (PCI) in the Cardiac Cath Lab of the Second Xiangya Hospital from January 2010 to December 2014. According to situation for cardiovascular events, patients were divided into 2 groups. The clinical factors were compared between the 2 groups.
 Results: The incidence of adverse event was 22% (67/304). By using t test and χ2 analysis, we found that Cr, NT-proBNP, HCT, WBC, age>75, Killip grade≥2, TIMI flow after PCI≤2, arrhythmia, multi-vessel lesion, ST-segment resolution≥50%, long D2B time are statistically different between the 2 groups. Logistic analysis revealed that HCT, NT-proBNP, Killip grade≥2, TIMI flow after PCI≤2, ST-segment resolution≥50%, long D2B time were important predictors for cardiac events in-hospital.
 Conclusion: HCT, NT-proBNP, Killip grade≥2, TIMI flow after PCI≤2, ST-segment resolution≥50%, long D2B time are important predictors for cardiac events in-hospital. The prognosis for AMI patient after emergency PCI could be improved and the incidence of cardiac event in hospital could be reduced if the high risk factors can be properly handled.

Spinal itch transmission has been reported to be mediated by at least two neuronal populations in spinal dorsal horn, neurons expressing brain-natriuretic peptide (BNP) receptor (Npra) and gastrin-releasing peptide (GRP) receptor (GRPR). Although Npra-expressing neurons were shown to be upstream of GRPR- expressing neurons in spinal itch transmission, the roles of BNP and GRP in the spinal neurotransmission of histamine-dependent and -independent itch remains unclear. Using in vivo electrophysiology and behavior analysis, this study examined the responses of chloroquine (histamine-independent pruritogen)-responsive and histamine-responsive dorsal horn neurons to spinal applications of BNP and GRP. Electrophysiologically, 9.5% of chloroquine-responsive neurons responded to BNP, 33.3% to GRP, and 4.8% to both, indicating that almost half of chloroquine-responsive neurons were unresponsive to both BNP and GRP. In contrast, histamine-responsive neurons did not respond to spinal BNP application, whereas 30% responded to spinal GRP application, indicating that 70% of histamine-responsive neurons were unresponsive to both BNP and GRP. Behavioral analyses showed differences in the time-course and frequency of scratching responses evoked by intrathecal BNP and GRP. These findings provide evidence that most BNP-Npra and GRP-GRPR signaling involve different pathways of spinal itch transmission, and that multiple neurotransmitters, in addition to BNP and GRP, are involved in spinal itch transmission. The electrophysiological results also suggest that spinal BNP contributes little to histaminergic itch directly., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

B-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPRA) and gastrin-releasing peptide (GRP)-GRP receptor (GRPR) systems contribute to spinal processing of itch. However, pharmacological and anatomic evidence of these two spinal ligand-receptor systems are still not clear. The aim of this study was to determine the spinal functions of BNP-NPRA and GRP-GRPR systems for regulating scratching activities in mice by using pharmacological and immunohistochemical approaches. Our results showed that intrathecal administration of BNP (0.3-3 nmol) dose dependently elicited scratching responses, which could be blocked by the NPRA antagonist (Arg6,β-cyclohexyl-Ala8,D-Tic16,Arg17,Cys18)-atrial natriuretic factor(6-18) amide (A71915). However, A71915 had no effect on intrathecal GRP-induced scratching. In contrast, pretreatment with a GRPR antagonist (D-Tpi6,Leu13ψ(CH2-NH)-Leu14)bombesin(6-14) (RC-3095) inhibited BNP-induced scratching. Immunostaining revealed that NPRA proteins colocalize with GRP, but not GRPR, in the superficial area of dorsal horn, whereas BNP proteins do not colocalize with either GRP or GRPR in the dorsal horn. Intradermal administration of ligands including endothelin-1, U-46619, bovine adrenal medulla 8-22, and Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL) increased scratching bouts at different levels of magnitude. Pretreatment with intrathecal A71915 did not affect scratching responses elicited by all four pruritogens, whereas pretreatment with RC-3095 only inhibited SLIGRL-induced scratching. Interestingly, immunostaining showed that RC-3095, but not A71915, inhibited SLIGRL-elicited c-Fos activation in the spinal dorsal horn, which was in line with behavioral outcomes. These findings demonstrate that: 1) BNP-NPRA system may function upstream of the GRP-GRPR system to regulate itch in the mouse spinal cord, and 2) both NPRA and GRPR antagonists may have antipruritic efficacy against centrally, but not peripherally, elicited itch., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: ATP-gated P2X3 receptors are important transducers of nociceptive stimuli and are almost exclusively expressed by sensory ganglion neurons. In mouse trigeminal ganglion (TG), P2X3 receptor function is unexpectedly enhanced by pharmacological block of natriuretic peptide receptor-A (NPR-A), outlining a potential inhibitory role of endogenous natriuretic peptides in nociception mediated by P2X3 receptors. Lack of change in P2X3 protein expression indicates a complex modulation whose mechanisms for downregulating P2X3 receptor function remain unclear., Results: To clarify this process in mouse TG cultures, we suppressed NPR-A signaling with either siRNA of the endogenous agonist BNP, or the NPR-A blocker anantin. Thus, we investigated changes in P2X3 receptor distribution in the lipid raft membrane compartment, their phosphorylation state, as well as their function with patch clamping. Delayed onset of P2X3 desensitization was one mechanism for the anantin-induced enhancement of P2X3 activity. Anantin application caused preferential P2X3 receptor redistribution to the lipid raft compartment and decreased P2X3 serine phosphorylation, two phenomena that were not interdependent. An inhibitor of cGMP-dependent protein kinase and siRNA-mediated knockdown of BNP mimicked the effect of anantin., Conclusions: We demonstrated that in mouse trigeminal neurons endogenous BNP acts on NPR-A receptors to determine constitutive depression of P2X3 receptor function. Tonic inhibition of P2X3 receptor activity by BNP/NPR-A/PKG pathways occurs via two distinct mechanisms: P2X3 serine phosphorylation and receptor redistribution to non-raft membrane compartments. This novel mechanism of receptor control might be a target for future studies aiming at decreasing dysregulated P2X3 receptor activity in chronic pain.

Chronic heart failure (CHF) is the final stage of various heart diseases, and is increasingly recognized as a major health problem in the elderly. Previous studies demonstrated that B‑type‑natriuretic peptide (BNP) is an established biomarker of CHF. Furthermore, BNP also regulates cell proliferation, differentiation and apoptosis. Recent evidence has revealed that BNP affects myocardial cell apoptosis during myocardial ischemia‑reperfusion injury. Long non‑coding RNAs (lncRNAs) are emerging as novel molecular compounds involved in gene regulation, and have important roles in numerous human diseases. However, the mechanism underlying the BNP and lncRNA-induced regulation of myocardial cell apoptosis remains to be elucidated. The present study reported that lncRNA LSINCT5, upregulated by BNP, is able to regulate myocardial cell apoptosis via the activation of the caspase‑1/interleukin (IL)‑1β signaling pathway. BNP-induced apoptosis of HCM cells was observed using flow cytometry, and involved caspase‑1. In addition, expression profiling using a human lncRNA polymerase chain reaction array revealed that LSINCT5 was highly expressed in BNP-treated myocardial cells, as compared with untreated cells. The role of lncRNA LSINCT5 in HCM cell apoptosis was also investigated. The results of the present study indicated that LSINCT5 silencing by small interfering RNA inhibits caspase‑1/IL‑1β signaling, and suppresses apoptosis in BNP-treated HCM cells. Therefore, high expression levels of BNP promote the apoptosis of myocardial cells through the lncRNA LSINCT5 mediator, which activates the caspase‑1/IL‑1β signaling pathway. These findings uncovered a novel pathogenic mechanism, and provided a potential therapeutic target for CHF.

Elevated B-type natriuretic peptide (BNP) regulates cGMP-phosphodiesterase activity. Its elevation is regarded as an early compensatory response to cardiac failure where it can facilitate sympathovagal balance and cardiorenal homeostasis. However, recent reports suggest a paradoxical proadrenergic action of BNP. Because phosphodiesterase activity is altered in cardiovascular disease, we tested the hypothesis that BNP might lose its efficacy by minimizing the action of cGMP on downstream pathways coupled to neurotransmission. BNP decreased norepinephrine release from atrial preparations in response to field stimulation and also significantly reduced the heart rate responses to sympathetic nerve stimulation in vitro. Using electrophysiological recording and fluorescence imaging, BNP also reduced the depolarization evoked calcium current and intracellular calcium transient in isolated cardiac sympathetic neurons. Pharmacological manipulations suggested that the reduction in the calcium transient was regulated by a cGMP/protein kinase G pathway. Fluorescence resonance energy transfer measurements for cAMP, and an immunoassay for cGMP, showed that BNP increased cGMP, but not cAMP. In addition, overexpression of phosphodiesterase 2A after adenoviral gene transfer markedly decreased BNP stimulation of cGMP and abrogated the BNP responses to the calcium current, intracellular calcium transient, and neurotransmitter release. These effects were reversed on inhibition of phosphodiesterase 2A. Moreover, phosphodiesterase 2A activity was significantly elevated in stellate neurons from the prohypertensive rat compared with the normotensive control. Our data suggest that abnormally high levels of phosphodiesterase 2A may provide a brake against the inhibitory action of BNP on sympathetic transmission., (© 2015 American Heart Association, Inc.)

Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood., (© 2015 American Heart Association, Inc.)

Background: The pathophysiology of orthostatic hypotension (OH) is multifactorial, with the most frequent causes being adverse effects of cardioactive drugs. In 20%-40% of cases, the etiology is unknown. In recent reports, altered levels of endogenous neuropeptides have been observed in noncardiac syncope, but B-type natriuretic peptide (BNP) and its amino-terminal cleavage fragment (NT-proBNP) have not been studied., Objective: The purpose of this study was to assess the possibility that BNP with its diuretic and vasorelaxant properties could contribute to OH., Methods: This prospective observational study comprised 85 consecutive OH subjects (58 women, age 49 ± 23 years) referred to a tertiary-care syncope clinic. All patients had normal left ventricular systolic and diastolic function, and clinical and laboratory findings consistent with euvolemia or modest hypovolemia. In 45 of 85 individuals (53%), an OH cause was determined., Results: Among the remaining 40 patients (21 women, age 57 ± 16 years) with OH of unknown cause, 6 of 40 (15%) exhibited unexpectedly elevated plasma NT-proBNP levels (14000, 5210, 2570, 7990, 3480, and 6680 pg/mL). In contrast, NT-proBNP values were normal (ie, <300 pg/mL) in the remaining 34 patients with OH of unknown cause and 45 patients with OH of known etiology. At 8 to 12 months of follow-up, volume repletion therapy requirements in patients with initial increased NT-proBNP diminished in conjunction with gradual fall of NT-proBNP concentrations., Conclusion: In select patients, markedly elevated levels of BNP or NT-proBNP may be associated with and possibly contribute to symptomatic OH., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Nesiritide, a recombinant form of B-type natriuretic peptide, is a vasodilator and currently recommended as an additive therapy for patients with acute decompensated heart failure (ADHF) who have been optimized on loop diuretics. With hospitalizations for ADHF rising, appropriate selection of therapy becomes even more important to optimize efficacy and reduce adverse events. Nesiritide has many properties that antagonize the pathophysiologic processes of heart failure and has demonstrated a comparative benefit in previous reports; however, controversy still remains with respect to its efficacy and safety. Based on results from recent clinical trials, nesiritide has been shown to be safe at currently approved doses and strongly considered for the treatment of ADHF in patients who remain symptomatic despite optimal doses of intravenous loop divertics.

Recent studies have shown that C-type natriuretic peptide (CNP) serves as a key control system during mouse oocyte maturation. We used pig models (in vitro and in vivo) to explore the role played by the natriuretic peptide family in porcine oocyte maturation. We reported the expression and location of natriuretic peptide system in different stages of porcine antral follicles. Atrial natriuretic peptide (ANP) and CNP were expressed primarily in granulosa cells, whereas brain natriuretic peptide (BNP) and natriuretic peptide receptor-B (NPRB) receptor were expressed in granulosa cells (both cumulus and mural granulosa cells) and thecal internal cells, and the natriuretic peptide receptor-A (NPRA) receptor predominantly in thecal cells. Upon in vitro culture, BNP and CNP maintained meiotic arrest of oocytes associated with cumulus cells. The expression levels of BNP, CNP, and the NPRB receptor increased upon treatment of prepubertal gilts with pregnant mare's serum gonadotropin and decreased upon subsequent human chorionic gonadotropin injection. Such dynamic changes in the expression of natriuretic peptides and their receptor paralleled the proportions of oocytes exhibiting nuclear maturation in vivo. These data indicated that BNP and CNP co-contributed to maintaining porcine meiotic arrest under physiological condition and lutenizing hormone (LH) relieved this inhibitory effect by decreasing the expression levels of BNP and CNP in vivo. Our present work, combined with previous data, improved the understanding of the oocyte meiotic arrest mechanisms and further revealed that natriuretic peptides serve as oocyte maturation inhibitor (OMI) to inhibit oocyte maturation in mammals., (© 2014 Wiley Periodicals, Inc.)

Previous studies suggest that B-type natriuretic peptide (BNP) exerts inhibitory effects on cardiac hypertrophy. Our studies have shown that long-term treatment of rats with BNP attenuated cardiac hypertrophy via down-regulation of TGF-β1 and up-regulation of smad7. However, the mechanisms have not been fully elucidated. In the present study, we examined the role of endogenous BNP on cardiomyocyte hypertrophy and the related molecular mechanisms. Cardiomyocytes from neonatal rats were cultured and a cardiomyocyte hypertrophy model was established with angiotensin II (Ang II). The effects of blockade of endogenous BNP by its receptor antagonist, HS-142-1, on cell hypertrophy were investigated. Cardiomyocyte hypertrophy indices, including cell surface area, protein content and [3H] incorporation were measured. Smad and mitogen-activated protein kinase (MAPK) protein expressions were detected using Western blot analysis. We found that HS-142-1 increased Ang II-stimulated cardiomyocyte hypertrophy and Smad activation. In addition, the increase of cardiomyocyte hypertrophy and the activation of Smad caused by HS-142-1 were not altered by the ERK inhibitor, PD98059, but were decreased by the p38 MAPK inhibitor, SB203580. These results demonstrate that endogenous BNP attenuates cardiomyocyte hypertrophy, and this may be mediated through p38 MAPK/Smad, but not ERK/Smad signaling pathway.

Objective: To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease., Approach and Results: In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting. Responsiveness of the various human adipose tissue depots to interleukin-6, tumor necrosis factor-α, and brain natriuretic peptide (BNP) was examined by using ex vivo models of human fat. The effects of inducible low-grade inflammation were tested by using the model of Salmonella typhi vaccine-induced inflammation in healthy individuals. In the cross-sectional study, HF strikingly increased adiponectin levels. Plasma BNP was the strongest predictor of circulating adiponectin and its release from all adipose tissue depots in patients with coronary artery bypass grafting, even in the absence of HF. Femoral AT was the depot with the least macrophages infiltration and the largest adipocyte cell size and the only responsive to systemic and ex vivo proinflammatory stimulation (effect reversible by BNP). Low-grade inflammation reduced circulating adiponectin levels, while circulating BNP remained unchanged., Conclusions: This study demonstrates the regional variability in the responsiveness of human adipose tissue to systemic inflammation and suggests that BNP (not systemic inflammation) is the main driver of circulating adiponectin in patients with advanced atherosclerosis even in the absence of HF. Any interpretation of circulating adiponectin as a biomarker should take into account the underlying disease state, background inflammation, and BNP levels., (© 2014 American Heart Association, Inc.)

Myometrial quiescence is a physiological stage of the myometrium during pregnancy. It is a period of active relaxation of the myometrial smooth muscle cells; myometrial quiescence is responsible for maintaining pregnancy. The precise mechanisms underlying myometrial quiescence have not been completely elucidated, although many mediators and cellular pathways have been described as playing a role. Fetal membranes (chorion and amnion) produce and release one or more substances that inhibit myometrial contractions, playing a central role in the maintenance of myometrial quiescence. Brain natriuretic peptide (BNP) is more potent than any other natriuretic peptide in inhibiting myometrial contractions in vitro. Brain natriuretic peptide is produced by the chorion and amnion, mainly during myometrial quiescence, and decreasing towards the end of pregnancy. Production of BNP is reduced in fetal membranes obtained from women in preterm labour. It is postulated that BNP, acting in a paracrine fashion, plays a key role in the maintaining myometrial quiescence and, therefore, controlling the duration of pregnancy. Furthermore, it is postulated that a premature decrease of BNP production by the fetal membranes may cause preterm labour and preterm birth.

Purpose of Review: To evaluate new development in the utility of brain natriuretic peptide and N-Terminal brain natriuretic peptide (BNP/NT-Pro-BNP) in the management of various cardiovascular diseases. The determination of plasma BNP levels has an established role in the discrimination of pulmonary oedema from other causes of acute dyspnoea, and there is increasing evidence of the utility of BNP/NT-Pro-BNP assay both as a prognostic tool in chronic heart failure and as a means of guiding therapy in heart failure patients aged below 70 years., Recent Findings: Findings have substantially extended the clinical utility of BNP/NT-Pro-BNP assay. In heart failure with preserved left ventricular ejection fraction, BNP elevation may also facilitate diagnosis, although its precise utility is uncertain.In the acute catecholamine-induced myocardial inflammatory condition of Tako-Tsubo cardiomyopathy (TTC), BNP/NT-Pro-BNP elevations are marked and persist for at least 3 months, despite the absence of pulmonary oedema. In TTC, BNP/NT-Pro-BNP therefore serves as an ancillary diagnostic measure as well as a marker of recovery. Among other conditions in which BNP assay may provide prognostic information are atrial fibrillation (in which the extent of elevation predicts thromboembolic risk) and pulmonary hypertension., Summary: BNP/NT-Pro-BNP assay has widespread utility as an adjunct to cardiovascular disease diagnosis and management.

C57BL/6 mice with dilated cardiomyopathy (DCM) were randomly divided to receive placebo or pitavastatin at a dose of 1 or 3 mg kg-1d-1. After 8 weeks treatment, mice with dilated cardiomyopathy developed serious cardiac dysfunction characterized by significantly enhanced left ventricular end-diastolic diameter (LVIDd), decreased left ventricular ejection fraction (LVEF) as well as left ventricular short axis fractional shortening (LVFS), accompanied with enlarged cardiomyocytes, and increased plasma levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) and plasma angiotensin II (AngII) concentration. Moreover, myocardium sarcoplasmic reticulum Ca2+ pump (SERCA-2) activity was decreased. The ratio of phosphorylated phospholamban (PLB) to total PLB decreased significantly with the down-regulation of SERCA- -2a and ryanodine receptor (RyR2) expression. Pitavastatin was found to ameliorate the cardiac dysfunction in mice with dilated cardiomyopathy by reversing the changes in the ratios of phosphorylated PLB to total PLB, SERCA-2a and RyR2 via reducing the plasma AngII concentration and the expressions of myocardium angiotensin II type 1 receptor (AT1R) and protein kinase C (PKC)b2. The possible underlying mechanism might be the regulation of myocardial AT1R-PKCb2-Ca2+ handling proteins.

The natriuretic peptide (NP) family includes atrial (ANP), brain or B-type (BNP) and C-type NP (CNP). A huge number of experimental and clinical studies, published in the 1st decade of this century, have added further support to the hypothesis that endocrine function in the human heart is a relevant component of a complex network including endocrine, nervous and immune systems. The NP hormones constitute a well-integrated regulatory system and share a similar spectrum of biological actions, although there are some differences in biological potency between ANP, BNP and CNP. However, several important issues on this field need to be investigated further. The production, secretion and peripheral degradation pathways of both BNP and CNP should be clarified in detail. In particular, the hypothesis that the circulating plasma pool of the prohormone can function as a precursor of the active peptide hormone should be demonstrated definitively. Recent findings indicate that peripheral processing of circulating prohormones could likely be submitted to regulatory rules, which might be impaired in patients with heart failure, opening up new perspectives even in the treatment of heart failure. This hypothesis suggests a novel pharmacological target for drugs inducing and/or modulating the maturation of the prohormone into active hormone., (© 2014 S. Karger AG, Basel.)

Plasma NT-proBNP has previously been evaluated in dogs with degenerative mitral valve disease (DMVD). However, reference intervals (RI) established according to the Clinical Laboratory and Standards Institute (CLSI) recommendations have never been provided. The objectives of this prospective study were to assess effects of breed, body weight, age, and sex on plasma NT-proBNP, and to establish RI according to CLSI for this biomarker in a large population of dogs predisposed to DMVD. 183 Healthy small-sized dogs from 7 breeds were included. Assays were performed by ELISA. Effects of covariates were tested using a general linear model. Although a sex effect was demonstrated (P=0.01), no significant effect of breed, body weight or age was shown. The proposed RI was 157-2842 pmol/L. 7% of dogs had plasma NT-proBNP >2617 pmol/L, and were considered as outliers despite normal cardiovascular examination. In conclusion, plasma NT-proBNP may be high in a few healthy small-sized dogs., (Crown Copyright © 2013. Published by Elsevier India Pvt Ltd. All rights reserved.)

Weaning patients from mechanical ventilation has been compared to a cardiac stress test. Weaning failure (WF) from a cardiac origin can be common in patients with limited cardiac reserve. Diuretic and vasodilator therapies are indicated for WF due to excessive preload, afterload, or myocardial ischemia. Alteration in intrathoracic pressure and lung volumes may also impact weaning process in a patient with poor cardiac function. Noninvasive ventilation decreases cardiac stress load and should be utilized in weaning patients with poor cardiac reserves. In fact, positive pressure therapy is now the standard of care for treating a patient with acute pulmonary edema and to decrease afterload (Frazier et al. Biol Res Nurs 2000; 1(4): 253-264; Pinsky MR. Chest 2005; 128(5 Suppl 2): 592S-597S.). Recently, biomarkers and echocardiography have been utilized to assess weaning success during spontaneous breathing trials. In this article, we describe the physiological alterations in cardiac and pulmonary systems during the weaning process and its impact on weaning outcome.

Left ventricular failure (LVF) is a clinical syndrome caused by abnormal systolic or diastolic function failing to meet the metabolic requirements of the body. It is important to diagnose and manage LVF in the earliest stages to prevent mortality and morbidity. This article extensively reviews the diagnostic, therapeutic, and prognostic utility of natriuretic peptides in LVF.

Cardiac natriuretic peptides (NP) are major activators of human fat cell lipolysis and have recently been shown to control brown fat thermogenesis. Here, we investigated the physiological role of NP on the oxidative metabolism of human skeletal muscle. NP receptor type A (NPRA) gene expression was positively correlated to mRNA levels of PPARγ coactivator-1α (PGC1A) and several oxidative phosphorylation (OXPHOS) genes in human skeletal muscle. Further, the expression of NPRA, PGC1A, and OXPHOS genes was coordinately upregulated in response to aerobic exercise training in human skeletal muscle. In human myotubes, NP induced PGC-1α and mitochondrial OXPHOS gene expression in a cyclic GMP-dependent manner. NP treatment increased OXPHOS protein expression, fat oxidation, and maximal respiration independent of substantial changes in mitochondrial proliferation and mass. Treatment of myotubes with NP recapitulated the effect of exercise training on muscle fat oxidative capacity in vivo. Collectively, these data show that activation of NP signaling in human skeletal muscle enhances mitochondrial oxidative metabolism and fat oxidation. We propose that NP could contribute to exercise training-induced improvement in skeletal muscle fat oxidative capacity in humans.

Natriuretic peptides, including BNP and CNP, elicit their effects via two guanylyl cyclase-linked receptors denoted NPR-A and NPR-B as well as a third receptor, NPR-C. The relative contributions of these receptors to the overall effects of NPs on heart rate (HR) and sinoatrial node (SAN) function are very poorly understood. The effects of BNP and CNP (10-500 nM) on HR and SAN myocyte spontaneous action potential (AP) firing were studied using wildtype mice and mice lacking functional NPR-C receptors (NPR-C(-/-)). In basal conditions and 10 nM doses of the β-adrenergic receptor (β-AR) agonist isoproterenol (ISO) BNP and CNP increased HR and AP firing in SAN myocytes. The NPR-C selective agonist cANF (10-500 nM) had no effects in basal conditions, but decreased HR and SAN AP frequency in the presence of ISO. These effects of cANF were completely absent in NPR-C(-/-) mice. Strikingly, in the presence of 1 μM doses of ISO, BNP and CNP switched to causing decreases in HR and SAN AP frequency. These decreases were not as large as those elicited by cANF and were absent in NPR-C(-/-) hearts, where BNP instead elicited a further increase in HR. Inhibition of NPR-A with A71915, in the presence of 1 μM ISO, enabled BNP to signal exclusively through NPR-C and to decrease HR as effectively as cANF. Together these data demonstrate that BNP and CNP affect HR and SAN function by activating multiple receptor subtypes. NPR-A/B mediate increases in HR and SAN function, but these effects are opposed by NPR-C, which plays an increasingly important signaling role in the presence of β-AR stimulation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: The brain needs continuous oxygen supply even in resting-state. Hypoxia enhances resting-state electroencephalographic (EEG) rhythms in the delta range, and reduces those in the alpha range, with a pattern similar to that observed in Alzheimer's disease (AD). Here we tested whether resting-state cortical EEG rhythms in patients with congestive heart failure (CHF), as a model of acute hypoxia, present frequency similarities with AD patients, comparable by cognitive status revealed by the mini mental state examination (MMSE)., Methods: Eyes-closed EEG data were recorded in 10 CHF patients, 20 AD patients, and 20 healthy elderly subjects (Nold) as controls. LORETA software estimated cortical EEG generators., Results: Compared to Nold, both AD and CHF groups presented higher delta (2-4Hz) and lower alpha (8-13Hz) temporal sources. The highest delta and lowest alpha sources were observed in CHF subjects. In these subjects, the global amplitude of delta sources correlated with brain natriuretic peptide (BNP) level in the blood, as a marker of disease severity., Conclusions: Resting-state delta and alpha rhythms suggest analogies between the effects of acute hypoxia and AD neurodegeneration on the cortical neurons' synchronization., Significance: Acute ischemic hypoxia could affect the mechanisms of cortical neural synchronization generating resting state EEG rhythms, inducing the "slowing" of EEG rhythms typically observed in AD patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) is primarily secreted by left ventricular (LV) stretch and wall tension. Notably, NT-pro-BNP is a prognostic marker in acute pulmonary embolism (PE), which primarily stresses the right ventricle (RV). We sought to evaluate the relative contribution of the RV to NT-pro-BNP levels during PE. A post-hoc analysis of an observational prospective outcome study in 113 consecutive patients with computed tomography (CT)-proven PE and 226 patients in whom PE was clinically suspected but ruled out by CT. In all patients RV and LV function was established by assessing ECG-triggered-CT measured ventricular end-diastolic-volumes and ejection fraction (EF). NT-pro-BNP was assessed in all patients. The correlation between RV and LV end-diastolic-volumes and systolic function was evaluated by multiple linear regression corrected for known confounders. In the PE cohort increased RVEF (β-coefficient (95% confidence interval [CI]) -0.044 (± -0.011); p<0.001) and higher RV end-diastolic-volume (β-coefficient 0.005 (± 0.001); p<0.001) were significantly correlated to NT-pro-BNP, while no correlation was found with LVEF (β-coefficient 0.005 (± 0.010); p=0.587) and LV end-diastolic-volume (β-coefficient -0.003 (± 0.002); p=0.074). In control patients without PE we found a strong correlation between NT-pro-BNP levels and LVEF (β-coefficient -0.027 (± -0.006); p<0.001) although not LV end-diastolic-volume (β-coefficient 0.001 (± 0.001); p=0.418). RVEF (β-coefficient -0.002 (± -0.006); p=0.802) and RV end-diastolic-volume (β-coefficient <0.001 (± 0.001); p=0.730) were not correlated in patients without PE. In PE patients, lower RVEF and higher RV end-diastolic-volume were significantly correlated to NT-pro-BNP levels as compared to control patients without PE. These observations provide pathophysiological ground for the well-known prognostic value of NT-pro-BNP in acute PE.

Aims: During heart failure (HF), the left ventricle (LV) releases B-type natriuretic peptide (BNP), possibly contributing to adverse cardiovascular events including ventricular arrhythmias (VAs) and LV remodelling. We investigated the cardiac effects of chronic BNP elevation in healthy mice and compared the results with a model of HF after myocardial infarction (PMI mice)., Methods and Results: Healthy mice were exposed to circulating BNP levels (BNP-Sham) similar to those measured in PMI mice. Telemetric surface electrocardiograms showed that in contrast with fibrotic PMI mice, electrical conduction was not affected in BNP-Sham mice. VAs were observed in both BNP-Sham and PMI but not in Sham mice. Analysis of heart rate variability indicated that chronic BNP infusion increased cardiac sympathetic tone. At the cellular level, BNP reduced Ca(2+) transients and impaired Ca(2+) reuptake in the sarcoplasmic reticulum, in line with blunted SR Ca(2+) ATPase 2a and S100A1 expression. BNP increased Ca(2+) spark frequency, reflecting Ca(2+) leak through ryanodine receptors, elevated diastolic Ca(2+), and promoted spontaneous Ca(2+) waves. Similar effects were observed in PMI mice. Most of these effects were reduced in BNP-Sham and PMI mice by the selective β1-adrenergic blocker metoprolol., Conclusion: Elevated BNP levels, by inducing sympathetic overdrive and altering Ca(2+) handling, promote adverse cardiac remodelling and VAs, which could account in part for the progression of HF after MI. The early use of β-blockers to prevent the deleterious effects of chronic BNP exposure may be beneficial in HF.

Background: The purpose of this study was to evaluate the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a predictor of disease progression in patients with pericardial effusions (PE)., Method: We retrospectively studied consecutive patients that had moderate or large PEs. Patients with pericardial events, such as reaccumulation of PE, persistent drainage through a catheter longer than one week, or newly developed constrictive pericarditis were defined as the progression group (Group A), and patients without these findings were defined as the group with no progression (Group B). The NT-proBNP assay was performed when PE was detected., Results: Compared to Group B (27 patients), Group A (15 patients) exhibited lower systolic and diastolic blood pressures (106 ± 13 vs. 118 ± 19 mm Hg, p=0.028; 69 ± 9 vs. 75 ± 11 mm Hg, p=0.047), higher NT-proBNP levels (1063 ± 756 vs. 578 ± 1090 ng/L, p=0.002), larger inferior vena cava (21 ± 6 vs. 17 ± 5 mm, p=0.039) and higher estimated right ventricular systolic pressure (37 ± 5 vs. 32 ± 6 mm Hg, p=0.024). NT-proBNP was the only independent predictor of disease progression (p=0.034) by multivariate regression analysis. The receiver-operating characteristic curve analysis showed that NT-proBNP values ≥ 548 ng/L demonstrated a sensitivity of 80% and a specificity of 78% for identifying disease progression (p=0.001)., Conclusions: The NT-proBNP value may predict disease progression in patients with PE. However, additional prospective studies with more patients are needed., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

BNP was discovered in the porcine brain extract in 1988. Subsequent studies have demonstrated that BNP is a cardiac hormone in humans. Plasma level of BNP is increased in patients with heart failure more than ANP. Therefore, BNP measurements as a biomarker for heart failure spread all over our country and all over the world. Now the guideline in the world recognizes that BNP is a useful biomarker for diagnosis for acute and chronic heart failure. However, the usefulness of "BNP-guided therapy for heart failure" is still controversial at present, because randomized-controlled studies have shown the neutral results. Although more than twenty years have passed since its discovery, recent studies have shown the new findings in BNP research. I describe here the recent advance of BNP research.

The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the actions of NPs on endothelial permeability and regeneration., (© 2012 The Author. British Journal of Pharmacology © 2012 The British Pharmacological Society.)

Natriuretic peptides (NPs) are best known for their ability to regulate blood vessel tone and kidney function whereas their electrophysiological effects on the heart are less clear. Here, we measured the effects of BNP and CNP on sinoatrial node (SAN) and atrial electrophysiology in isolated hearts as well as isolated SAN and right atrial myocytes from mice. BNP and CNP dose-dependently increased heart rate and conduction through the heart as indicated by reductions in R-R interval, P wave duration and P-R interval on ECGs. In conjunction with these ECG changes BNP and CNP (100 nM) increased spontaneous action potential frequency in isolated SAN myocytes by increasing L-type Ca(2+) current (I(Ca,L)) and the hyperpolarization-activated current (I(f)). BNP had no effect on right atrial myocyte APs in basal conditions; however, in the presence of isoproterenol (10nM), BNP increased atrial AP duration and I(Ca,L). Quantitative gene expression and immunocytochemistry data show that all three NP receptors (NPR-A, NPR-B and NPR-C) are expressed in the SAN and atrium. The effects of BNP and CNP on SAN and right atrial myocytes were maintained in mutant mice lacking functional NPR-C receptors and blocked by the NPR-A antagonist A71915 indicating that BNP and CNP function through their guanylyl cyclase-linked receptors. Our data also show that the effects of BNP and CNP are completely absent in the presence of the phosphodiesterase 3 inhibitor milrinone. Based on these data we conclude that NPs can increase heart rate and electrical conduction by activating the guanylyl cyclase-linked NPR-A and NPR-B receptors and inhibiting PDE3 activity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

B-type natriuretic peptide (BNP) is a plasma marker of left ventricular dysfunction and cardiac volume overload. Currently it is mainly used in the cardiovascular field. BNP is an intrinsic regulator of the embryonic stem cell proliferation, and the reduction in BNP can increase the apoptosis rate. The epitope of N terminal pro-brain natriuretic peptide-BNP is most stable. BNP1-32 has the strongest biological activity but with lower plasma level in heart failure patients. The plasma BNP level plays an important role in the diagnosis, prognosis, hospital admission and mortality of heart failure, and can be used as a monitoring indicator in the treatment of heart failure. The deficiency of corin enzyme in patients with heart failure can cause the increase of cracking pro-BNP. BNP can also provide diagnostic and prognostic information for other populations and diseases. Genetic studies on BNP and its receptors also provide important information. Nesiritide, neutral endopeptidase inhibitors, and vasopeptidase inhibitors of the natriuretic peptide synthesis have been used for the treatment of cardiovascular disorders. However, more reliable and accurate approaches for detecting BNP and N terminal pro-brain natriuretic peptide-BNP require further investigations.

Objective: The authors hypothesized that preoperative N-terminal probrain natriuretic peptide (NT-proBNP) correlates well with longitudinal strain measurements and with Doppler measurements of diastolic function., Design: Prospective observational study., Setting: University teaching hospital., Participants: Forty patients undergoing elective cardiac surgery., Interventions: Aortic valve replacement, coronary artery bypass grafting, or a combination of these procedures., Measurements and Main Results: Plasma NT-proBNP concentration was obtained by analyzing blood samples with a commercially available kit. Left ventricular systolic function was assessed by speckle tracking ultrasound strain measurements and left ventricular diastolic function was assessed by 2 Doppler methods: E/A ratio and E/E' ratio. Tissue Doppler imaging velocities (E' and A') were measured in the basal septum (annular) and pulse-wave Doppler was used to measure mitral in-flow profile (E and A). The correlation between global strain data from the speckle tracking ultrasound measurement and NT-proBNP levels was ρ = 0.35 (p = 0.026). With a cutoff value of -15% in global strain measurements, there was a significant difference in NT-proBNP levels (117 v 57 pg/mL, p = 0.048). E/E' values correlated with NT-proBNP levels (ρ = 0.46, p = 0.011). With a cutoff of 15 in E/E' values, there were significant differences in corresponding NT-proBNP levels (33 v 113 pg/mL, p = 0.004)., Conclusions: A correlation was found between plasma levels of NT-proBNP and speckle tracking ultrasound strain measurements by an easily employed method applicable in the anesthesia and preoperative settings. In addition, the well-established marker of diastolic function, E/E', correlated well with NT-proBNP, whereas the E/A ratio failed to show any association., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Adiponectin was reported recently to have roles in the pathophysiology of preeclampsia. Moreover, elevation of adiponectin and brain natriuretic peptide (BNP) has been observed in preeclampsia. We examined the possible links between adiponectin and BNP in the pathophysiology of preeclampsia. We performed a cross-sectional study in 56 preeclampsia patients and 56 controls matched for gestational age and body mass index. The BNP, leptin, and adiponectin levels were measured by ELISA, and their mRNA expressions were evaluated in omental adipose tissue by real-time PCR. The effects of BNP on adiponectin and leptin mRNA expression and secretion were investigated in primary cultures of adipocytes from obese and normal-weight women. The BNP, adiponectin, and leptin levels were significantly higher in preeclampsia patients compared with controls. The adiponectin level was increased significantly in normal-weight preeclampsia patients compared with overweight preeclampsia patients. Adiponectin mRNA expression was increased significantly in adipose tissues of preeclampsia patients compared with controls and was also increased significantly in normal-weight preeclampsia patients compared with overweight preeclampsia patients, whereas leptin was not. BNP and adiponectin showed significant positive correlations in both normal-weight and overweight preeclampsia patients. BNP had a significantly weaker effect on adiponectin in overweight compared with normal-weight preeclampsia patients. Moreover, BNP had a weaker effect on adiponectin production in adipocytes from overweight women compared with adipocytes from normal-weight women using primary culture of human adipocytes. These data suggested that BNP may play a role in hyperadiponectinemia of preeclampsia patients. The weaker effect of BNP on adiponectin production may participate in the pathophysiology of overweight preeclampsia patients.

Heart Failure (HF) is characterized by activation inflammatory mediators that contributes to the disease progression. Brain natriuretic peptide (BNP) plasma levels increase in HF with a prognostic significance. The aim of this study was to evaluate the expression and activity of inducible nitric oxide synthase (iNOS) in peripheral blood mononuclear cell (PBMC) extracted from patients and a possible linear correlation between iNOS and plasma levels of BNP in decompensated chronic HF (DCHF) patients. To establish the DCHF, thirty-five male patients were evaluated. All patients were venesected within 24 h of admission to exclude an inflammatory state through evaluation of c-reactive protein. Only twenty subjects showed symptoms of DCHF were included in the study. Other patients were included in the control group. In DCHF, left ventricular ejection fraction (LVEF) percent was reduced and systolic pulmonary artery pressure (PAPs) was increased. Furthermore, iNOS expression and BNP plasma levels were significantly higher in patients with DCHF as compared to controls group. These findings indicate that in DCHF patients, iNOS activity exhibits a significant linear correlation with plasmatic BNP level.