心房利钠肽分泌的肾上腺素能受体调节

心房利钠肽(Atrial natriaretic peptide,ANP)或称心房利钠因子(Atria natriuretic factor,ANF)是哺乳动物心房肌细胞合成,储存和释放的肽类激素,由28个氨基酸组成。在血循环中它有强大的排钠、利尿、扩张血管和降压作用,并能使     

利尿钠肽在诊断心力衰竭中的应用价值

探讨利尿钠肽的水平对心力衰竭（心衰）早期诊断的应用价值。采用放免法、ELISA法检测了129例心衰患者血浆中的心房利尿钠肽（ANP）、脑利尿钠肽（BNP）、N末端脑钠肽前体蛋白（NT-proBNP）水平,并与30例健康对照者进行了比较分析。结果显示,心衰患者血浆中的ANP、BNP、NT-proBNP显著高于健康对照组,且均随着NYHA分级的升高而逐渐增加,其含量在NYHA Ⅳ级时到达最高,心衰患者的血浆ANP、NT-proBNP水平与LVEF呈明显负相关。检测血浆中的ANP、BNP、NT-proBNP含量简便、快捷,可用于心衰诊断及NYHA分级判断。     

脑钠肽RIA在心血管疾病诊治中的应用

脑钠肽(Brain natriuretic peptide,BNP)是Sudoh等1988年首先从猪脑中分离纯化出来的一种肽类激素,亦称B型尿钠肽,它是继心钠肽(atrial natriuretic peptide,ANP)后被发现在心血管疾病中起重要作用的又一利钠肽激素。BNPRIA建立后,越来越引起临床医生的高度重视,在广泛应用于心血管疾病的诊治中,对其研究探讨取得了不少进展,现综述如下。     

B型钠尿肽的研究进展

型钠尿肽(B-type natriutetic peptide，BNP)是1988年由日本学者从猪脑内分离出来的一种利钠多肽，又称脑钠肽(Brain natriutetic peptide)。与心房肽(ANP)相似，具有利尿、利钠、扩张血管和降压作用，是心钠素家族中的新成员。它是一种主要由心室合成、分泌的心脏激素。能敏感而特异地反映左心室功能变化，在心血管疾病的发病、诊断、治疗以及预后等方面均有重要的意义。本文就其生化、生理和临床应用进展综述如下。     

脑利钠肽评估充血性心力衰竭患者的临床应用

脑利钠肽（brain natriuretic peptide，BNP）是继心钠素之后发现在心血管疾病中起重要作用的又一利钠系统成员^[1]，是心室容量扩张和压力负荷增加时由心室释放的一种心脏神经激素，具有利尿、利钠效应，能舒张血管，抑制醛固酮分泌和肾素活性。本研究评价血BNP作为血标志物在心力衰竭时的浓度变化，并探讨其临床诊断价值。     

甲状腺激素与心脏、冠脉微血管及脑钠肽和N端脑钠肽激素原关系的研究现状

随着人们对甲状腺激素（TH）病理生理的深入了解，发现心脏是TH（包括T3、T4）作用的主要靶器官，TH可通过直接或间接作用引起心脏结构和（或）功能改变。脑钠肽（Brain Natriuretic Peptide，BNP）是一种由心室合成、分泌的心脏激素，属于利钠肽系统。BNP与心功能密切相关，作为心脏神经激素，起到利钠、利尿、降压和舒张血管平滑肌作用。N端脑钠肽激素（NT-proBNP）与BNP来源于同一前体，有研究证实TH可促使其分泌增加。     

大肠杆菌β-半乳糖苷酶ED片段与人B型钠尿肽抗原的共表达

B型钠尿肽(B-type natriuretic peptide,BNP)又称脑钠肽(brain natriuretic peptide),是心室分泌的激素样短肽,具有利尿利钠效应,能够舒张血管、抑制醛固酮分泌及肾素活性[1].血浆BNP水平已被证实是充血性心力衰竭诊断和预后判断的生物标志物.     

心力衰竭时的钠利尿肽系统

心力衰竭时的钠利尿肽系统心钠素（ＡＮＰ）、脑钠素（ＢＮＰ）和Ｃ型钠利尿肽（ＣＮＰ）是结构相关的一族多肽。ＡＮＰ为２８个氨基酸的多肽，由心房分泌，具有利尿利钠、血管活性和抑制肾素的作用。ＢＮＰ为３２个氨基酸的多肽，也存在于心脏，具有与ＡＮＰ相似的结构和...     

CNP/NPR-B/cGMP信号通路调控雌性生殖过程

C型利钠肽(C-type natriuretic peptide,CNP)与其特异性受体利钠肽受体B(natriuretic peptide receptor B,NPR-B)结合并催化下游第二信使环磷酸鸟苷(cyclic guanosinc monophosphate,cGMP)生成,形成CNP/NPR-B/cGMP信号通路,从而介导多种生物学效应.近年来大量研究证实,CNP/NPR-B/cGMP信号通路与卵泡发育、卵母细胞减数分裂与成熟及胚胎着床和发育关系密切,提示此信号通路可能在雌性生殖过程中发挥显著作用.     

心房肽-Ⅲ与大鼠肾脏受体膜制备的特异性结合

心房肽是心脏分泌的一类激素,具有强大的利尿利钠作用,其中以心房肽Ⅲ的作用最强。关于心房肽利尿利钠的机制,目前还不十分清楚。本工作应用标记的~(125)Ⅰ-心房肽-Ⅲ,证明在大鼠肾脏含有特异性心房肽受体。     

Origin and characterization of atrial natriuretic peptide in the rat parotid gland

Summary The heart atria represent the major site of synthesis for atrial natriuretic peptide (ANP) which exerts potent natriuretic, diuretic and vasoactive functions. Recently, ANP-immunoreactivity has been detected in extracardial organs involved in water and electrolyte homeostasis, such as the intestine and certain exocrine glands. The present study investigates ANP in the parotid gland. It was found by immunohistochemical techniques that the peptide is localized in ductal cells of the gland. An analysis of the immunoreactive material by high-pressure liquid chromatography and radioimmunoassay revealed the prohormone of ANP (ANP 1-126) and the biologically active fragment (ANP 99-126). Furthermore, Northern blot hybridization disclosed the presence of mRNA coding for ANP. It is suggested that ANP is synthesized and released from the parotid gland and functions in the control of saliva production.     

Impaired renal responsiveness to human atrial natriuretic peptide (hANP) in normotensive patients with type 1 diabetes mellitus

Summary Potential impairment of the efficacy of human atrial natiuretic peptide (human ANF-(99-126), hANP), the most potent endogenous natriuretic agent in healthy subjects, was examined in eight male normotensive patients with uncomplicated type 1 diabetes mellitus (aged 22–37 years). After giving informed consent, patients and eight male control subjects (aged 22–28 years) received in a random double-blind study design i.v. bolus injections of 100 µg hANP (Bissendorf peptide) or placebo. At base-line, patients differed from controls in elevated creatinine clearance (P<0.05) and in mild postprandial hyperglycemia. Whereas the responses of urinary cyclic guanosine monophosphate, the second messenger of hANP, were found to be normal in patients, the diuretic and natriuretic effects of hANP were grossly impaired when compared to controls (P<0.01); hANP resulted in increased plasma protein concentrations only in controls (P<0.05 vs patients). In both groups, creatinine clearance remained uninfluenced by hANP. There were similar decreases in plasma renin activity, aldosterone, levels, and blood pressure (systolic more than diastolic) in both groups (P<0.05 vs placebo). Heart rate and blood glucose remained unchanged. Thus, there is evidence for a decreased responsiveness to hANP exclusively of renal fluid, sodium, and chloride excretion in uncomplicated type 1 diabetes mellitus. The mechanisms responsible for this phenomenon remain obscure, neither a down regulation at the hANP receptor sites nor an hANP-induced shift from intra- to extravascular fluid volume are likely to be involved in its probably diabetes-specific pathogenesis.Abbreviations cGMP Cyclic guanosine monophosphate - hANP Human atrial natriuretic peptide - human ANF-(99-126) Human atrial natriuretic factor-(99-126)     

Development and application of a urodilatin (CDD/ANP-95#x2013;126)-specific radioimmunoassay

Urodilatin, a renal natriuretic peptide that is an analogue to circulating atrial natriuretic peptide [-ANP (99-126)], is measurable with a highly specific and sensitive radioimmunoassay. While most ANP antibodies cannot distinguish between urodilatin and other ANP analogues, the polyclonal urodilatin antibody specifically measures human urodilatin without any cross-reactivity to other ANP analogues. Urodilatin is not detected in blood from healthy volunteers nor from cardiac patients. Urinary urodilatin accounts for only a part of total urinary ANP immunoreactivity. Urodilatin excretion closely parallels sodium excretion in response to an acute volume load while changes in urinary immunoreactive ANP excretion do not reflect this renal response. We conclude that specific urodilatin assays are required to explore further the physiological role of the renal natriuretic peptide.     

Atrial amyloid deposits in the failing human heart display both atrial and brain natriuretic peptide-like immunoreactivity

Atrial amyloid deposits are common in the ageing human heart and contain alpha-atrial natriuretic peptide (proANP99-126) immunoreactivity. However, atrial myocytes secrete both amino and carboxy terminal fragments of the ANP prohormone (proANP1-126) and also express an homologous, but separate brain natriuretic peptide (BNP). Characteristic amyloid deposits were identified in the atria of 9/22 patients (26-63 years of age) with end-stage heart failure. Amyloid fibrils displayed immunoreactivity for both amino and carboxy terminal fragments of proANP1-126 and for the distinct BNP sequence. As in other endocrine organs, both mature and precursor peptide sequences appear to be constituents of amyloid fibrils. Whilst immunoreactivity for cardiac peptide hormones is co-localized in atrial amyloid deposits, it is uncertain whether the increase in natriuretic peptide expression which accompanies cardiac failure contributes to the incidence of isolated atrial amyloidosis.     

Natriuretic peptides increase a K+ conductance in rat mesangial cells

Mesangial cells (MC) are a main target of natriuretic peptides in the kidney and are thought to play a role in regulating glomerular filtration rate. We examined the influence of cGMP-generating (i.e. guanosine 3,5-cyclicmonophosphate) peptides on membrane voltages (V_m) of rat MC by using the fast whole-cell patch-clamp technique. The cGMP-generating peptides were tested at maximal concentrations ranging from 140 to 300 nmol/1. Whereas human CNP (C natriuretic peptide), rat guanylin and human uroguanylin had no significant effect on V_m of these cells, human BNP (brain natriuretic peptide), rat CDD/ANP-99-126 (cardiodilatin/atrial natriuretic peptide) and rat CDD/ANP-95-126 (urodilatin) hyperpolarized V_m significantly by 1.6 ± 0.4 mV (BNP,n = 8), 3.7 ± 0.3 mV (CDD/ANP-99-126,n = 25) and 2.8 ± 0.4 mV (urodilatin,n = 9), respectively. The half-maximally effective concentration (EC₅₀) for the latter two was around 400 pmol/l each. This hyperpolarization could be mimicked with 0.5 mmol/1 8-bromo-guanosine 3,5-cyclic monophosphate (8-Br-cGMP) and was blocked by 5 mmol/1 Ba²⁺. The K⁺ channel blocker 293 B (1O)) mol/l) depolarized basal V_m by 4.3 ± 0.4 mV (n = 8), but failed to inhibit the hyperpolarization induced by CDD/ANP-99-126 (160 nmol/1) (n = 8). The K⁺ channel opener cromakalim (10 mol/1) neither influenced basal V_m nor altered the hyperpolarization induced by 160 nmol/1 CDD/ANP-99-126 (n = 8). Adenosine (100 mol/1) hyperpolarized V_m by 13.4 ± 1.3 mV (n = 16). At 100 mol/1, 293 B did not inhibit the adenosine-induced hyperpolarization (n = 6). At 160 nmol/l, CDD/ANP-99-126 enhanced the adenosine-induced hyperpolarization significantly by 1.5 ± 0.6 mV (n = 10). CDD/ANP-99-126 (160 nmol/1) failed to modulate the value to which V_m depolarized in the presence of 1 nmol/l angiotensin II (n = 10), but accelerated the repolarization to basal V_m, by 49 ± 20% (n = 8). These results indicate that the natriuretic peptides CDD/ANP-99-126, CDD/ANP-95-126 and BNP hyperpolarize rat MC probably due to an increase of a K⁺ conductance. This effect modulates the voltage response induced by angiotensin II. The natriuretic-peptide-activated conductance can be blocked by Ba²⁺, but not by 293 B and cannot be activated by cromakalim. This increase in the K⁺ conductance seems to be additive to that inducable by adenosine, indicating that different K⁺ channels are activated by these hormones.     

Natriuretic peptides and genesis of asthma: an emerging paradigm?

Exposure to allergens and infections contribute to early immune development. However, knowledge of the role of cellular metabolic, physiologic, and endocrinologic factors in controlling immune development and asthma is limited. Immune cells, including macrophages, dendritic cells, and T lymphocytes, express receptors for atrial natriuretic peptide (ANP) both in the fetal and neonatal lymphoid organs. ANP has garnered much attention for its cardiovascular effects, but its apparently significant role in the physiology and immunity of the lung has been underappreciated. Studies indicate that ANP also plays a significant role in shaping the early immune responses to environmental antigens. The C-terminal prohormone natriuretic peptide ANP (or NP(99-126)), which possesses bronchodilatory properties, is involved in polarizing dendritic cells to produce a T(H)2 response. Also, de novo overexpression of another pro-ANP peptide, NP(73-102), provides persistent bronchoprotection and induces significant anti-inflammatory activities in the lung epithelial cells. Thus natriuretic peptides appear to play a pivotal role in the genesis and control of asthma, and they might provide an important target to modulate allergen-induced immune responses in allergic patients.     

Characterization of the 5′-flanking region and chromosomal assignment of the human brain natriuretic peptide gene

Brain natriuretic peptide (BNP) is a cardiac hormone that occurs predominantly in the ventricle, and synthesis and secretion of BNP are greatly augmented in patients with congestive heart failure and in animal models of ventricular hypertrophy. In order to elucidate the molecular mechanisms underlying the human BNP gene expression in the heart, the human BNP gene was isolated from a size-selected genomic minilibrary. The 1.9-kb human BNP 5-flanking region (–1813 to +110) contained an array of putative cis-acting regulatory elements. Various lengths of the cloned 5-flanking sequences were linked upstream to the bacterial chloramphenicol acetyltransferase (CAT) gene, and their promoter activities were assayed. The 1.9-kb promoter region showed a high-level CAT activity in cultured neonatal rat ventricular cardiocytes. When the CT-rich sequences (–1288 to –1095) were deleted, the high-level activity was reduced to approximately 30%. The 399-bp BNP 5 flanking region (–289 to +110) showed approximately 10% activity of the 1.9-kb region. Furthermore, using human-rodent somatic hybrid cell lines, the BNP gene was assigned to human chromosome 1, on which the atrial natriuretic peptide gene is localized. The present study leads to a better understanding of the molecular mechanisms for the human BNP gene expression in the heart.Abbreviations ANP Atrial natriuretic peptide - AP-1 Activator protein-1 - BNP Brain natriuretic peptide - CAT Chloramphenicol acetyltransferase     

C-type natriuretic peptide decreases hippocampal network oscillations in adult rats in vitro

C-type natriuretic peptide (CNP) is an abundant neuropeptide in the human brain and the cerebrospinal fluid. CNP is involved in anxiogenesis and exerts its effects through the natriuretic peptide receptor B (NPR-B), which is expressed in the hippocampus. Hippocampal network oscillations of distinct frequency bands like gamma (γ)-oscillations and sharp wave-ripple complexes (SPW-Rs) are likely involved in various cognitive functions such as the storage of information and memory consolidation in vivo. Here, we tested the effects of CNP on distinct network oscillations in horizontal slices of rat hippocampus. We found that CNP decreased the power of stimulus- and ACh/physostigmine-induced γ-oscillations. In contrast to stimulus-induced γ-oscillations, CNP increased the frequency of ACh-induced, persistent network oscillations. Moreover, the peptide hormone reduced the incidence of LTP-associated SPW-Rs in area CA3 and CA1. Immunohistochemistry indicates that the peptide binds to receptors expressed on a subset of GAD 65–67-immunopositive cells in addition to binding to principal and other presumably non-neuronal cells. CNP caused a hyperpolarization of CA3 neurons increased their input resistance and decreased inhibitory conductance. Together, our data suggest that the effects of CNP on synchronized hippocampal network oscillations might involve effects on hippocampal interneurons.     

Expression and glucocorticoid regulation of natriuretic peptide clearance receptor (NPR-C) mRNA in rat brain and choroid plexus

The natriuretic peptide clearance receptor (NPR-C) binds atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide with high affinity. This receptor lacks an intracellular guanylate cyclase domain, and is believed to exert biological actions by sequestration of released natriuretic peptides and/or inhibition of adenylate cyclase. The present report summarizes the first detailed mapping of NPR-C mRNA in rat brain. In situ hybridization analysis revealed high levels of NPR-C mRNA expression in frontal and retrosplenial granular cortices, medial preoptic nucleus, ventral cochlear nucleus and choroid plexus. NPR-C mRNA expression was also observed in deep layers of neocortex and limbic cortex, posterior cortical amygdala, ventral subiculum, amygdalohippocampal area, and dentate gyrus. Positive hybridization signal was observed in both anterior and intermediate lobes of the pituitary gland. Regulatory studies indicated that expression of NPR-C mRNA was increased in the medial preoptic nucleus of adrenalectomized rats, suggesting negative glucocorticoid regulation. No changes in NPR-C mRNA expression were observed in frontal cortex or choroid plexus. These results suggest a role for the NPR-C in modulation of natriuretic peptide availability and/or adenylate cyclase activity in a subset of central natriuretic peptide circuits concerned with cortical, olfactory and neuroendocrine functions. Response of the NPR-C gene to changes in circulating hormones suggests the capacity for glucocorticoid modulation of natriuretic peptide action at the receptor level.