Atrial natriuretic peptide inhibits angiotensin-stimulated proximal tubular sodium and water reabsorption

The discovery that atrial extracts have potent diuretic and natriuretic properties revealed a possible endocrine function of the heart in the regulation of extracellular fluid volume. Since that first report intense research activity has been directed towards determining the mechanism of action of the active atrial natriuretic polypeptides (ANP) found in these extracts. Despite these efforts it remains controversial whether the renal actions of ANP are exerted solely on the process of glomerular filtration or involve additional direct actions on tubular transport. We have investigated the possibility that atrial natriuretic polypeptides may induce natriuresis by suppression of proximal tubular sodium and water reabsorption. Using shrinking split-drop micropuncture combined with simultaneous capillary perfusion in anaesthetized rats we report that 20 nanomolar alpha-rANP (the main component of ANP in rat plasma) added to the peritubular fluid had no direct effect on proximal fluid uptake whereas picomolar angiotensin II had a marked stimulatory action as reported. The stimulatory effect of angiotensin II on fluid reabsorption was inhibited by peritubular ANP at physiological concentrations and abolished by higher concentrations of ANP. Thus at physiological concentrations ANP acts within the kidney to decrease proximal reabsorption by inhibition of angiotensin-stimulated sodium and water transport.     

Structure of the dimerized hormone-binding domain of a guanylyl-cyclase-coupled receptor

The atrial natriuretic peptide (ANP) hormone is secreted by the heart in response to an increase in blood pressure. ANP exhibits several potent anti-hypertensive actions in the kidney, adrenal gland and vascular system. These actions are induced by hormone binding extracellularly to the ANP receptor, thereby activating its intracellular guanylyl cyclase domain for the production of cyclic GMP. Here we present the crystal structure of the glycosylated dimerized hormone-binding domain of the ANP receptor at 2.0-A resolution. The monomer comprises two interconnected subdomains, each encompassing a central beta-sheet flanked by alpha-helices, and exhibits the type I periplasmic binding protein fold. Dimerization is mediated by the juxtaposition of four parallel helices, arranged two by two, which brings the two protruding carboxy termini into close relative proximity. From affinity labelling and mutagenesis studies, the ANP-binding site maps to the side of the dimer crevice and extends to near the dimer interface. A conserved chloride-binding site is located in the membrane distal domain, and we found that hormone binding is chloride dependent. These studies suggest mechanisms for hormone activation and the allostery of the ANP receptor.     

A new natriuretic peptide in porcine brain

Atrial natriuretic peptide (ANP), a hormone secreted from mammalian atria, regulates the homoeostatic balance of body fluid and blood pressure. ANP-like immunoreactivity is also present in the brain, suggesting that the peptide functions as a neuropeptide. We report here identification in porcine brain of a novel peptide of 26 amino-acid residues, eliciting a pharmacological spectrum very similar to that of ANP, such as natriuretic-diuretic, hypotensive and chick rectum relaxant activities. The complete amino-acid sequence determined for the peptide is remarkably similar to but definitely distinct from the known sequence of ANP, indicating that the genes for the two are distinct. Thus, we have designated the peptide 'brain natriuretic peptide' (BNP). The occurrence of BNP with ANP in mammalian brain suggests the possibility that the physiological functions so far thought to be mediated by ANP may be regulated through a dual mechanism involving both ANP and BNP.     

Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy

In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.     

Purification, sequencing and synthesis of natriuretic and vasoactive rat atrial peptide

Mammalian atria contain potent natriuretic and diuretic substances which exist in high- and low-molecular-weight forms and which appear to be associated with atrium-specific granules. The natriuretic effect of atrial extract is largely accountable for by its renal haemodynamic effects; atrial extracts also antagonize hormone- and non-hormone-induced contraction of the isolated rabbit aorta and isolated rat kidney vasculature. We have completely purified a low-molecular-weight natriuretic and vasoactive substance from rat atria and characterized it as a 24-amino acid peptide. Synthetic peptide, produced by solid-phase synthesis, mimics biological effects of crude atrial extract and purified peptide; its activity is enhanced by slow oxidation, suggesting a disulphide (Cys 4-Cys 20) configuration for the native peptide. If secreted into blood, this atrial natriuretic peptide (' auriculin B') could be a novel peptide hormone of considerable importance to renal and cardiovascular homeostasis.     

A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor

Atrial natriuretic peptide (ANP) is a polypeptide hormone whose effects include the induction of diuresis, natriuresis and vasorelaxation. One of the earliest events following binding of ANP to receptors on target cells is an increase in cyclic GMP concentration, indicating that this nucleotide might act as a mediator of the physiological effects of the hormone. Guanylate cyclase exists in at least two different molecular forms: a soluble haem-containing enzyme consisting of two subunits and a non-haem-containing transmembrane protein having a single subunit. It is the membrane form of guanylate cyclase that is activated following binding of ANP to target cells. We report here the isolation, sequence and expression of a complementary DNA clone encoding the membrane form of guanylate cyclase from rat brain. Transfection of this cDNA into cultured mammalian cells results in expression of guanylate cyclase activity and ANP-binding activity. The ANP receptor/guanylate cyclase represents a new class of mammalian cell-surface receptors which contain an extracellular ligand-binding domain and an intracellular guanylate cyclase catalytic domain.     

Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases

Alpha atrial natriuretic peptide (alpha-ANP) and brain natriuretic peptide are homologous polypeptide hormones involved in the regulation of fluid and electrolyte homeostasis. These two natriuretic peptides apparently share common receptors and stimulate the intracellular production of cyclic GMP as a second messenger. Molecular cloning has defined two types of natriuretic peptide receptors: the ANP-C receptor of relative molecular mass (Mr) 60-70,000 (60-70 K), which is not coupled to cGMP production and may function in the clearance of ANP and the ANP-A receptor of Mr 120-140 K, which is a membrane form of guanylate cyclase in which ligand binding to the extracellular domain activates the cytoplasmic domain of the enzyme. Here we report the cloning and expression of a second human natriuretic peptide-receptor guanylate cyclase, the ANP-B receptor. The ANP-B receptor is preferentially activated by porcine brain natriuretic peptide rather than human alpha-ANP, whereas the ANP-A receptor responds similarly to both natriuretic peptides. These observations may have important implications for our understanding of the central and peripheral control of cardiovascular homeostasis.     

心房钠尿肽在大鼠肾缺血-再灌注损伤中的体外抗氧化作用研究

目的：探讨心房钠尿肽在大鼠肾缺血-再灌注损伤中的体外抗氧化作用。方法：建立大鼠肾缺血-再灌注模型,测定心房钠尿肽温浴处理前后各组肾组织匀浆液中SOD活性和MDA含量变化。结果：肾组织匀浆液中MDA含量在实验组显著低于实验对照组（P值〈0．05）,SOD活性无明显变化。结论：心房钠尿肽直接清除缺血-再灌注损伤中生成的MDA,对大鼠肾缺血再灌注损伤有一定抗氧化保护作用。     

伤口收缩及瘢痕攣缩的机制

本文通过复习伤口收缩及瘢痕收缩的有关文献和通过有关病理标本的观察,指出伤口收缩与瘢痕收缩是两个过程,并认为两者收缩的机制不同。目前伤口收缩机制的假说主要有肌纤维母细胞说,伤口内容物说和肌肉收缩说。通过比较,作者认为肌肉收缩说比较合理。关于瘢痕挛缩机制的学说,目前文献已否定胶原纤维老化收缩学说,只提肌纤维母细胞学说。通过观察有广泛瘢痕病变的标本(如门脉性肝硬化,原发及继发性肾固缩等),未发现有病变器官的主质细胞和血管由于瘢痕组织收缩而导致的萎缩和受压现象。作者认为,这些病变器官及瘢痕缩小的主要机制是由于病灶内主质细胞的丢失,以及肉芽组织及瘢痕组织内充血血管不再充血、数量减少,以及其间质水肿液消退所引起的。     

The search for new cardiovascular biomarkers

Despite considerable advances in the treatment of cardiovascular disease, it remains the leading cause of death in developed countries. Assessment of classic cardiovascular risk factors--including high blood pressure, diabetes and smoking--has a central role in disease prevention. However, many individuals with coronary heart disease (a narrowing of the blood vessels that supply the heart) have only one, or none, of the classic risk factors. Thus, new biomarkers are needed to augment the information obtained from traditional indicators and to illuminate disease mechanisms.     

绿色供应链管理的战略决策模型

由于利益相关者对环境的日益关注,环境战略已逐渐融入到组织战略和日常的运作管理中,而供应链范围内实施绿色化战略显得更为重要.对绿色供应链管理战略决策的要素及相互关系进行了补充和完善,形成了新的战略决策框架模型.考虑到框架结构的网状性,采用Saaty提出的ANP分析工具,用实例说明了采用ANP法进行绿色供应链管理战略决策的过程.     

Renal cytochrome P450-related arachidonate metabolite inhibits (Na+ + K+)ATPase

The function of the nephron, the anatomical unit of the kidney, is segmented; at least 12 segments have been identified that differ in their morphology, transport properties and hormonal responsiveness. The medullary portion of the thick ascending limb of the loop of Henle (mTALH) has one of the highest concentrations of (Na+ + K+)ATPase found in mammalian tissues, reflecting the importance of this nephron segment in the regulation of extracellular fluid volume, as active sodium transport is driven by (Na+ + K+)ATPase. Here, in cells derived primarily from the mTALH of the outer medulla of rabbit kidney, we have identified a cytochrome P450-dependent monooxygenase system which metabolizes arachidonic acid to two biologically active oxygenated products; one of the products inhibits (Na+ + K+)ATPase and the other relaxes blood vessels. We report that formation of these oxygenated arachidonate metabolites is stimulated by arginine vasopressin (AVP) and salmon calcitonin (SCT).     

The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm

The nephron is the basic structural and functional unit of the vertebrate kidney. It is composed of a glomerulus, the site of ultrafiltration, and a renal tubule, along which the filtrate is modified. Although widely regarded as a vertebrate adaptation, 'nephron-like' features can be found in the excretory systems of many invertebrates, raising the possibility that components of the vertebrate excretory system were inherited from their invertebrate ancestors. Here we show that the insect nephrocyte has remarkable anatomical, molecular and functional similarity to the glomerular podocyte, a cell in the vertebrate kidney that forms the main size-selective barrier as blood is ultrafiltered to make urine. In particular, both cell types possess a specialized filtration diaphragm, known as the slit diaphragm in podocytes or the nephrocyte diaphragm in nephrocytes. We find that fly (Drosophila melanogaster) orthologues of the major constituents of the slit diaphragm, including nephrin, NEPH1 (also known as KIRREL), CD2AP, ZO-1 (TJP1) and podocin, are expressed in the nephrocyte and form a complex of interacting proteins that closely mirrors the vertebrate slit diaphragm complex. Furthermore, we find that the nephrocyte diaphragm is completely lost in flies lacking the orthologues of nephrin or NEPH1-a phenotype resembling loss of the slit diaphragm in the absence of either nephrin (as in human congenital nephrotic syndrome of the Finnish type, NPHS1) or NEPH1. These changes markedly impair filtration function in the nephrocyte. The similarities we describe between invertebrate nephrocytes and vertebrate podocytes provide evidence suggesting that the two cell types are evolutionarily related, and establish the nephrocyte as a simple model in which to study podocyte biology and podocyte-associated diseases.     

糖尿病血瘀证与内皮素和心钠素的关系研究

目的 :探讨内皮素 (ET)、心钠素 (ANP)与糖尿病 (DM)血瘀证的关系。方法 :检测 44例 DM血瘀证患者和 2 0例正常对照组的 ET和 ANP含量。结果 :血瘀证组 ET、ANP含量明显高于正常对照组。结论 :ET、ANP共同参与了 DM血瘀证的病理过程     

mRNA sequence for human cardiodilatin-atrial natriuretic factor precursor and regulation of precursor mRNA in rat atria

The mammalian cardiac atrium has recently been shown to contain numerous peptides that exert marked effects on kidney function and vascular resistance. With one exception, the peptides have potent natriuretic and diuretic activities, and sequence similarities suggest that they may be derived from a common atrial natriuretic factor (ANF) precursor. The exception, cardiodilatin (CDD), differs from the ANF peptides in possessing potent vasorelaxant activity, but not natriuretic and diuretic activities. Here we report the cloning and sequence analysis of the cDNA for the human precursor protein (preproCDD-ANF) containing both the CDD and ANF sequences. The CDD sequence represents the N-terminal sequence preceded directly by a signal peptide, while the ANF sequence is present at the C-terminal end of the protein. Using hybridization analysis, we further show that the amount of rat preproCDD-ANF mRNA, which is synthesized selectively in the atria but not the ventricles, markedly decreases on water deprivation, suggesting that the water-electrolyte balance may be an important factor in the regulation of the expression of the preproCDD-ANF gene.     

基于多重分形去趋势波动分析的视网膜图像分割

引入善于描述非稳定图像的多重去趋势波动理论,提出一种基于多重去趋势分析的视网膜图像分割方法.该方法采用直方图均衡化对图像进行预处理来增强血管影像,然后采用多重去趋势波动分析计算图像的广义赫斯特指数,并利用血管指数特性来分割血管,最后用形态学进行图像后处理,得到最终的血管图像.基于DIARETDE0和DIARETDE1两个数据库进行实验.结果表明,该方法在处理视网膜病变图像时有较好的完整性和连通性,能够较好地提取血管主体,具有很好的临床应用价值.     

血液灌流联合血液滤过治疗急性重症白毒伞蕈中毒临床分析

目的：探讨血液灌流联合血液滤过治疗白毒伞蕈中毒的临床价值。方法：对我院2004年6月至8月集中收治的进行血液灌流联合血液滤过治疗的13例急性重症白毒伞蕈中毒患者进行回顾性分析。对13例患者治疗前后肝、肾功能、心肌酶及临床症状进行对比观察。结果：13例患者在应用血液灌流联合血液滤过治疗后,血液中血尿素氮（BUN）、血肌酐（SCr）、肌酸激酶同工酶（CK—MB）、丙氨酸氨基转移酶（ALT）、天门冬酸氨基转移酶（AST）、乳酸脱氢酶（LDH）明显下降,其中BUN、SCr、CK—MB具有统计学意义（P〈0．05）。临床症状明显改善,除2例患者由于经济原因未坚持治疗自动出院、1例因多器官功能衰竭死亡外,其余10例全部治愈出院。结论：对于急性重症白毒伞蕈中毒的救治,早期及时行血液灌流联合血液滤过治疗,可有效地清除和吸附血液中BUN、SCr、CK—MB、ALT、AST、LDH毒性物质,是避免白毒伞蕈中毒发生致死性肝损害的有效措施之一。     

Inhibition of aldosterone production in the adrenal glomerulosa by atrial natriuretic factor

Several forms of the polypeptide atrial natriuretic factor (ANF) have been isolated recently from rat and human atria and identified; they are probably associated with the secretory granules of atrial tissue. The potent ability of ANFs to increase urine sodium content is mediated by their direct action on the kidney. We report here the high intrinsic activity of a synthetic replicate of one form of this molecule, ANF(8-33)(ref. 7), to inhibit directly basal aldosterone secretion and its ability to antagonize the stimulatory effects of adrenocorticotropin (ACTH) and angiotensin II (AN-II) on the secretion of aldosterone by rat adrenoglomerulosa cells in vitro. Our results suggest that ANF is of clinical importance in the management of aldosterone-dependent hypertension by modifying the adrenocortical response to endogenous ACTH and AN-II.     

肾功能对心肌酶谱的影响

为了了解肾功能是否对血清心肌酶谱有影响,笔者对226例慢性肾脏病例的肾小球滤过率和血清心肌酶谱的检测结果进行了相关分析.结果表明:肾小球滤过率与所测的心肌酶谱为不相关关系(P>0.05).对于慢性肾脏病患者,心肌酶谱仍是有意义的判断指标.     

青光眼滤过术后浅前房原因分析

目的：探讨青光眼滤过性手术后浅前房形成的原因、治疗和预防．方法：随机选择了276例300只青光眼患者，就青光眼滤过性手术后浅前房的原因作回顾性分析．结果：本组浅前房发生率14．33％．浅前房形成的原因有滤过作用过强18只眼（41．86％），脉络膜脱离15只眼（34．88％），房水渗漏9只眼（20．93％），恶性青光眼1只跟（2．33％）．结论：滤过作用过强和脉络膜脱离是浅前房形成的主要原因．浅前房不能完全预防。但可减少其发生，最重要的一步是在手术结束时前房是否形成，前房如果未形成，应找出原因及时处理．