脑利钠肽的生理特性及其重组脑利钠肽在急性心力衰竭治疗中的应用

心脏分泌两个重要的利钠肽：心房肌细胞分泌的心房利钠肽（atrial natriuretic peptide，ANP）和心室肌细胞分泌的脑利钠肽（brain natriuretic peptide，BNP）。当心房和心室壁张力改变时，心肌细胞释放ANP和BNP，从而发挥平稳的扩血管、排钠作用，同时能抑制交感神经系统和肾素-血管紧张素-醛固酮系统。据报道BNP是评估心血管疾病危险性的重要生化标志物，BNP浓度的增高能预测急性冠状动脉综合征和心力衰竭病人短期及长期心脏性死亡的危险性。近年来，合成的重组人BNP能模拟内源性BNP的作用，用于治疗急性心力衰竭。     

B型利钠肽在呼吸系统疾病中的临床应用研究进展

B型利钠肽（B—typenatriureticpeptide,BNP）又称脑钠肽（brain natriuretic peptide）,是一种多肽类激素,主要由心室肌细胞合成和分泌,以应对心脏容量和压力负荷的变化。B型利钠肽和氨基末端B型利钠肽（N—terminalpro—B—type natriuretic peptide,NT-proBNP）前体最先被应用于心力衰竭的临床诊断、     

氮末端脑利钠肽与急性冠脉综合征的关系

脑利钠肽(brain natriuretic peptide,BNP)是“心脏激素”利钠肽家族成员之一。利钠肽家族包括心房利钠肽(atrialnatriuretic peptide,ANP)、BNP、C型利钠肽(C-type natriuret-ic peptide CNP)、D型利钠肽(D-type natriuretic peptide,DNP)和V型利钠肽(V-type natriuretic peptide,VNP)。它们都有类似的环状结构,但氨基端和羧基端结构不相同,因此具有不同的生理功能。BNP最先从猪脑中发现,后来又在人的心脏中分离纯化出且发现其分泌量高于脑。N-TproBNP(N-terminal pro-B-type natriuretic peptide)是BNP激素原分裂后没有活…     

脑利尿钠肽用于心血管疾病的诊治进展

1981年由de Bold等发现的心房利尿钠肽(ANP)拓展了人们的观念:即心脏不仅是一个机械泵而且还是一个神经内分泌器官.20年来围绕着利尿钠肽家族进行了大量的科学研究,脑利尿钠肽(Brain natriuretic peptide BNP)、C型利钠肽(Ctype natriuretic peptide CNP)及树眼镜蛇利尿钠肽(Dendroaspis natriuretic peptide DNP)相继被发现.     

脑利尿钠肽在心血管疾病中的研究进展

脑利尿钠肽（brain natriurelic peptide，BNP），又称B型利钠肽，是利尿钠肽家族中的一员。这个家族还包括心房利尿钠肽（atrial natriuretic peptide，ANP）、C型利钠肽（C—type natriuretic peptide，CNP）及树眼镜蛇利尿钠肽（dendroaspis natriuretic peptide，DNP）。BNP是1988年由日本学者Sodoh等首先从猪脑中分离纯化，主要由心室合成和分泌。心室负荷和室壁张力的改变是刺激BNP分泌的主要条件。BNP对于调控心血管的血流动力学、心室重构、水钠平衡具有重要作用，也是机体抵御血容量超负荷的重要因素及心肌源性的抗纤维化因子。本文就目前关于BNP在心血管疾病诊断与治疗方面的研究进展综述如下。     

血浆利尿钠肽与心房颤动关系的研究进展

循环利尿钠肽家族由心房钠尿肽(atrial natriuretic peptide,ANP)、脑钠肽(B-type natriuretic peptide,BNP)、C-型利尿钠肽(CNP)及树眼镜蛇属利尿钠肽组成。在正常状态下,ANP、BNP和CNP主要在心房产生,ANP和BNP合成和分泌的主要刺激是心室壁张力。就实验检测:ANP前体(proANP)与成熟ANP相比半减期更长,且由于其为激素前体物质、没有相关的作用受体、胞间或蛋白间的相互作用小、分子量大、在血浆中的稳定性高,因此被认为是比成熟ANP更     

急性心肌梗死脑利钠肽变化及预后价值

利钠肽系统主要包括心房利钠肽(atrial natriuretic peptide,ANP)、B型利钠肽(B-type natriuretic peptide,BNP)、C型利钠肽(C-type natriuretic peptide,CNP)和D型利钠肽(D-type natriuretic peptide,DNP),其中BNP在心力衰竭诊断、危险分层、治疗指导和预后判断等各方面的作用已得到肯定.本文综述急性心肌梗死(AMI)后血浆BNP水平变化及规律,及对临床AMI治疗和预后判断的价值.     

BNP和NT-proBNP在慢性阻塞性肺疾病合并肺动脉高压中的临床研究进展

脑钠肽（brain natriuretic peptide,BNP）和N末端脑钠肽前体（N-terminal pro-brain natriuretic peptide,NT-pro-BNP）作为心衰标志物,在心力衰竭诊断方面的应用已比较明确,近年来研究表明,BNP和NT-proBNP作为生物标志物在慢性阻塞性肺疾病（COPD）合并肺动脉高压（PAH）诊断及预后判断方面有重要价值.本文对BNP和NT-proBNP在COPD合并PAH的研究进展进行综述.     

脑钠肽在心力衰竭诊断治疗中的应用进展

脑钠肽(brain natriuretic peptide,BNP)是利钠肽家族(natriuretic peptide family)的主要成员之一,可在脑组织中检出,但主要由心室肌细胞合成和释放[1].人的脑钠肽前体(proBNP)含有108个氨基酸[2],经裂解形成由32个氨基酸肽链组成的BNP和无生物学活性的碎片(NT-proBNP,含76个氨基酸,图1).     

利钠肽类激素在心律失常后的变化

目的观察心房利钠肽（atrial natriuretic peptide，ANP）、脑钠肽（brain natriuretic peptide，BNP）和C-型利钠肽（C-type natriuretic peptide，CNP）在心律失常后的变化，并探讨3者是否具有相关性。方法各种病因导致心律失常患者22例（NYHA心功能分级〈Ⅱ级），并设正常对照组20例，用竞争性放射免疫分析法测定血浆中ANP、BNP和CNP浓度。结果心律失常组血浆BNP较正常对照组明显升高，差异具有显著性（p〈0．01），而血浆ANP和CNP差异不具有显著性（p〉0．05）。心律失常组患者血浆ANP、BNP与CNP不具有相关性。结论无心力衰竭患者发作心律失常后血浆BNP可能明显升高，而血浆ANP与CNP浓度无明显变化。     

The role of natriuretic peptides in cardioprotection

Atrial natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP) are circulating hormones of cardiac origin that play an important role in the regulation of intravascular blood volume and vascular tone. The plasma concentrations of ANP and BNP are elevated in heart failure, and they are considered to compensate for heart failure because of their diuretic, natriuretic, and vasodilating actions and inhibitory effects on renin and aldosterone secretion. Evidence is also accumulating from recent work that ANP and BNP exert their cardioprotective functions not only as circulating hormones but also as local autocrine and/or paracrine factors. In studies using cultured neonatal myocytes and fibroblasts, exogenous administration of both ANP and ANP antagonists demonstrated that ANP has antihypertrophic and antifibrotic functions. Corroborating these in vitro results, mice lacking natriuretic receptor-A (NPR-A), the receptor for ANP and BNP, develop cardiac hypertrophy and fibrosis independent of their blood pressure. Recent studies also suggest that the intracardiac natriuretic peptides/cGMP system plays a counter-regulatory role against the intracardiac renin-angiotensin-aldosterone system and TGF-beta mediated pathway. In a clinical setting, human recombinant ANP and BNP may be used for a therapy of heart failure; however, further evaluation is required in the future.     

Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides

The mammalian natriuretic peptide family consists of atrial (ANP), brain [B-type; BNP] and C-type natriuretic peptide (CNP) and three receptors, natriuretic receptors-A (NPR-A), -B (NPR-B) and -C (NPR-C). Both ANP and BNP are abundantly expressed in the heart and are secreted mainly from the atria and ventricles, respectively. By contrast, CNP is mainly expressed in the central nervous system, bone and vasculature. Plasma concentrations of both ANP and BNP are elevated in patients with cardiovascular disease, though the magnitude of the increase in BNP is usually greater than the increase in ANP. This makes BNP is a clinically useful diagnostic marker for several pathophysiological conditions, including heart failure, ventricular remodeling and pulmonary hypertension, among others. Recent studies have shown that in addition to BNP-32, proBNP-108 also circulates in human plasma and that levels of both forms are increased in heart failure. Furthermore, proBNP-108 is O-glycosylated and circulates at higher levels in patients with severe heart failure. In this review we discuss recent progress in our understanding of the biochemistry, molecular biology and clinical relevance of the natriuretic peptide system.     

Associations between plasma natriuretic peptides and echocardiographic abnormalities in geriatric outpatients

Identification of patients with cardiac dysfunction can be difficult in the geriatric population. Recently, different subtypes of the natriuretic peptide family have been advocated as biomarker for the diagnosis of heart failure in the emergency department setting. In this study we looked at associations between natriuretic peptide plasma levels and echocardiographic abnormalities in geriatric outpatients. Two-dimensional transthoracic echocardiography was performed in 209 community-dwelling subjects, visiting the geriatric outpatient clinic of our university hospital. Subjects were 65 years or older and had no markedly impaired cognitive function. Mean atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) plasma levels were respectively 11.0 and 10.8pmol/l. BNP, but not ANP correlated with left ventricular dysfunction and left ventricular mass, whereas both peptides correlated with left atrial dimension and valvular lesions. A natriuretic peptide level in the highest tertile was associated with a higher risk of any echocardiographic abnormality, with odds ratios for BNP of 7.15 (range 2.15-23.71), and for ANP of 3.07 (range 1.15-8.16). In conclusion, elevated BNP and ANP plasma levels are closely related to cardiac abnormalities in elderly subjects. The association between cardiac abnormalities and natriuretic peptides is stronger for BNP than for ANP, hence for detection of cardiac abnormalities measurement of BNP plasma values are preferred over ANP plasma values.     

Minireview: natriuretic peptides during development of the fetal heart and circulation

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones, secreted by the atria and ventricles, respectively, in the normal adult heart. They participate in the regulation of blood pressure and body fluid homeostasis and modify growth and development of cardiovascular tissues and bone. Levels of ANP are higher in the fetal circulation than in adults, and fetal ventricles express higher levels of ANP and BNP than adult ventricles. The reappearance of ventricular ANP expression in adults is recognized as a marker of the induction of the embryonic gene program in ventricular hypertrophy. The natriuretic peptide system appears to be functional by midgestation, to respond to volume stimuli, and to regulate blood pressure and salt and water balance in the developing embryo. In addition, the natriuretic peptides may help regulate the blood supply to the fetus, acting as vasodilators in the placental vasculature. Peaks of ANP and BNP expression during gestation coincide with significant events in cardiac organogenesis, suggesting a role for ANP/BNP in the formation of the heart. In knockout mice lacking the natriuretic peptide receptor (NPR)-A gene (Npr1(-/-)), survival is reduced, with hearts enlarged at birth and possible cardiac developmental abnormalities. Surviving adult Npr1(-/-) mice have elevated blood pressure and marked cardiac hypertrophy and fibrosis, indicating that the ANP/BNP system is an important regulator of myocyte growth during development.     

Natriuretic peptide family]

The natriuretic peptide system consists of at least three endogenous ligands: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and three receptors, ANP-A receptor (guanylate cyclase A), ANP-B receptor (guanylate cyclase B) and clearance receptor (C receptor). ANP, the prototype of natriuretic peptides, is mainly produced in the atrium and secreted into the circulation as a cardiac hormone. ANP is also produced in the ventricle and in the central nervous system. BNP, first isolated from the porcine brain, has a marked divergence in its molecular size and sequence among species. In humans and rats, the major site of production of BNP is the ventricle of the heart. BNP is also secreted into the circulation as a cardiac hormone. The plasma BNP level in normal subjects is approximately one sixths of the plasma ANP level; however, the plasma BNP level markedly increases in heart failure, renal failure and hypertension and the augmentation of the BNP secretion is much larger than that of the ANP secretion. In addition, clearance of BNP from the circulation is slower than that of ANP. Furthermore, BNP is secreted more urgently than ANP in acute heart failure. CNP distributes mainly in the central nervous system and pituitary gland. No significant amount of CNP is detectable in the heart and plasma. Thus, CNP is a local regulator rather than a cardiac hormone. Three natriuretic receptors have ligand selectivity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma brain natriuretic peptide and atria natriuretic peptide as predictors for diastolic heart failure in patients with type 2 diabetes mellitus

Objective To study the change of diastolic cardiac function in diabetic patients and to determine the diagnostic value of plasma brain natriuretic peptide （BNP） and atria natriuretic peptide （ANP） for diastolic heart failure in patients with type 2 diabetes mellitus. Methods Twelve healthy subjects and seventy-one diabetic patients were included in the study. Plasma BNP and ANP were measured with immtmoradiometic assay. Results Plasma levels of BNP and ANP increased significantly with increased severity of diastolic heart dysfunction. The ratio of E/A had significant negative correlation with the plasma levels ofBNP （r=0.669,P〈0.001） and ANP （r=0.579, P〈0.01）. AUC of ANP and BNP in ROC model was 91.9% and 65.3%, respectively. Conclusions The plasma level of BNP might be a valuable predictor for differential diagnosis of diastolic cardiac function in diabetic patients.     

利钠肽的心脏保护作用

心钠肽和脑钠肽作为心源性循环激素在调节血容量和血管张力方面具有重要作用,近年研究显示他们不仅作为循环激素而且作为局部自分泌和/或旁分泌因子发挥心脏保护作用,如抗心肌肥厚和抗纤维化作用。另外,利钠肽/cGMP系统在心力衰竭、心肌梗死及心肌缺血/再灌注损伤的病理生理中具有重要作用。最近,人类重组心钠肽和脑钠肽用于临床心力衰竭治疗已取得一定进展。现就以上做一综述。     

Expression of A-, B-, and C-type natriuretic peptide genes in failing and developing human ventricles. Correlation with expression of the Ca(2+)-ATPase gene.

Brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are novel natriuretic peptides, originally isolated from porcine brain. Similar to atrial natriuretic peptide (ANP), BNP is also synthesized in and secreted from cardiocytes, but CNP is not expressed at significant levels in normal adult myocardium. Previous studies have indicated that the serum level and ventricular expression of the ANP gene were augmented in patients with heart failure. Recently, the serum level of BNP was also reported to increase in human heart failure. To examine whether or not the expression of these natriuretic peptides is regulated in ventricular myocardium in a concordant manner, we performed Northern blot analysis using total cellular RNA isolated from the diseased left ventricles of 30 cardiac transplant recipients with end-stage heart failure, seven ventricles from organ donors (control group), and two ventricles of artificially aborted 17- and 19-week-old fetuses. The levels of mRNAs encoding both BNP and ANP increased significantly (p less than 0.01) in the left ventricular myocardium from the patients with end-stage heart failure as compared with the control group. The levels of BNP mRNA correlated positively with those of ANP mRNA (r = 0.73, p less than 0.01) and negatively with those of sarcoplasmic reticulum Ca(2+)-ATPase mRNA (r = -0.66, p less than 0.01) in the left ventricular myocardium from the patients with heart failure. There was also a negative correlation between the levels of ANP and the sarcoplasmic reticulum Ca(2+)-ATPase mRNAs (r = -0.65, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic peptide and brain natriuretic peptide coexist in the secretory granules of human cardiac myocytes.

To elucidate the intracellular localization of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in human cardiac myocytes, an immunocytochemical study was carried out by a double immunogold technique using antisera highly specific for ANP and BNP. Surgical and autoptic tissue specimens of human heart were studied. In the atrial myocytes, ANP was localized in almost all of the secretory granules, whereas BNP was colocalized with ANP in some of the granules. Although very few secretory granules were observed in ventricular myocytes, colocalization of ANP and BNP was basically the same as in atrial myocytes. No immunoreactive products were found in the control studies. These results suggest that secretion of BNP is under a regulatory mechanism similar to that of ANP.