B-type natriuretic peptide (BNP), not ANP, is the principal cardiac natriuretic peptide in vertebrates as revealed by comparative studies

The natriuretic peptide (NP) family consists of at least seven members; cardiac ANP, BNP and VNP and brain CNPs (CNP1-4). Phylogenetic and comparative genomic analyses showed that CNP4 is the ancestral molecule of the family, from which CNP3 and CNP1/2 were duplicated in this order, and that the three cardiac NPs were generated from CNP3 by tandem duplication. Seven members existed at the divergence of ray-finned fishes and lobe-finned fishes (tetrapods), but some of the NP genes have disappeared during the course of evolution. In ray-finned fishes, all three cardiac NPs exist in chondrostei and some migratory teleost species, but VNP is generally absent and ANP is absent in a group of teleosts (Beloniformes). In tetrapods, ANP and BNP are present in mammals and amphibians, but ANP is usually absent in reptiles and birds. Thus, BNP is a ubiquitous cardiac NP in bony fishes and tetrapods though elasmobranchs and cyclostomes have only CNP3/4 as a cardiac NP.Functional studies indicate that cardiac NPs are essential Na⁺-extruding hormones throughout vertebrates; they play critical roles in seawater (SW) adaptation in teleosts, while they are important volume-depleting hormones in mammals as water and Na⁺ are regulated in parallel in terrestrial animals. In mammals, cardiac NPs become prominent in pathological conditions such as heart failure where they are used in diagnosis and treatment. Although the functional role of BNP has not yet been fully elucidated compared with ANP in non-mammalian vertebrates, it appears that BNP plays pivotal roles in the cardiovascular and body fluid regulation as shown in mammals. ANP has previously been recognized as the principal cardiac NP in mammals and teleosts, but comparative studies have revealed that BNP is the only cardiac NP that exists in all tetrapods and teleosts. This is an excellent example showing that comparative studies have created new insights into the molecular and functional evolution of a hormone family.     

A perspective on the role of natriuretic peptides in amphibian osmoregulation

The natriuretic peptide (NP) system is a complex family of peptides and receptors that is primarily linked to the maintenance of osmotic and cardiovascular homeostasis. In amphibians, the potential role(s) of NPs is complicated by the range of osmoregulatory strategies found in amphibians, and the different tissues that participate in osmoregulation. Atrial NP, brain NP, and C-type NP have been isolated or cloned from a number of species, which has enabled physiological studies to be performed with homologous peptides. In addition, three types of NP receptors have been cloned and partially characterised. Natriuretic peptides are always potent vasodilators in amphibian blood vessels, and ANP has been shown to increase the permeability of the microcirculation. In the perfused kidney, ANP causes vasodilation, diuresis and natriuresis that are caused by an increased GFR rather than effects in the renal tubules. These data are supported by the presence of ANP receptors only on the glomeruli and renal blood vessels. In the bladder and skin, the function of NPs is enigmatic because physiological analysis of the effects of ANP on bladder and skin function has yielded conflicting data with no clear role for NPs being revealed. Overall, NPs often have no direct effect, but in some studies they have been shown to inhibit the function of AVT. In addition, there is evidence that ANP can inhibit salt retention in amphibians since it can inhibit the ability of adrenocorticotrophic hormone or angiotensin II to stimulate corticosteroid secretion. It is proposed that an important role for cardiac NPs could be in the control of hypervolaemia during periods of rapid rehydration, which occurs in terrestrial amphibians.     

Identification of a natriuretic peptide (NP) in cyclostomes (lamprey and hagfish): CNP-4 is the ancestral gene of the NP family

In bony fishes, natriuretic peptides (NPs) comprise a hormone family that is composed of seven subtypes; ANP, BNP, VNP that have an intramolecular ring and N- and C-terminal extensions, and four CNPs (CNP-1 to -4) that lack the C-terminal extension. To assess the ancestral molecule of the NP family, we determined the NP sequences in several species of two extant cyclosotome groups, lampreys and hagfishes. A cDNA encoding CNP was cloned from the heart and brain of three phylogenetically distant species of lampreys, Geotria australis, Lampetra japonica, and Petromyzon marinus. In the deduced prohormone sequence of each species, two potential processing signals, lysine-lysine (KK) that is commonly present in CNP precursors, and arginine-X-X-arginine (RXXR) for furin-like proprotein convertase (PC) that is typical for CNP-4 were present. The deduced mature peptides that are released at each signal were highly conserved among three species; 100% cleaved at KK and >92% processed at RXXR. In L. japonica, the CNP gene was expressed almost exclusively in the heart and brain. Meanwhile, a cDNA encoding NP with a C-terminal tail sequence was cloned from the heart and brain of three hagfish species in different genera, Myxine glutinosa, Eptatretus cirrhatus, and Paramyxine atami. The precursor sequences including the prosegment had >80% identity among the three hagfish species. A processing signal, RXXR, is also conserved in the prosegment of all hagfish NPs. The molecular phylogenetic analyses inferred that the lamprey CNP and hagfish NP belong to the CNP-4 group, even though the hagfish NP has a C-terminal sequence extended from the intramolecular ring. The presence of a processing signal, RXXR, in the prosegment of cyclostome NPs supports the above classification. Based on the current findings, we suggest that the ancestral gene of the NP family is CNP-4.     

Bradykinin-related peptides and tryptophyllins in the skin secretions of the most primitive extant frog, Ascaphus truei

The tailed frog Ascaphus truei occupies a unique position in phylogeny as the most primitive extant anuran and is regarded as the sister taxon to the clade of all other living frogs. A previous study led to the isolation of eight antimicrobial peptides, termed ascaphins, from norepinephrine-stimulated skin secretions. Peptidomic analysis (HPLC separation followed by MALDI mass spectrometry and Edman degradation) of these secretions has led to the identification and structural characterization of 13 additional peptides present in relatively high concentration. In addition to bradykinin (BK; RPPGFSPFR), a C-terminally extended bradykinin (peptide RD-11; RPPGFSPFRVD), a bradykinin-like peptide (peptide AR-10; APVPGLSPFR), and a C-terminally extended form of this peptide (peptide AV-12; APVPGLSPFRVV) were obtained in pure form. These peptides produced concentration-dependent relaxation of precontracted mouse tracheal rings with a rank order of potency of BK>RD-11>AR-10>AV-12 but only RD-11 caused the same maximal relaxation as bradykinin. Four small peptides were also isolated from the skin secretions that contain the Pro-Trp motif that is a characteristic of the tryptophyllin family of peptides previously identified in skins of frogs of the family Hylidae. The data show that the synthesis of dermal peptides that may play a role in defense against predators arose early in the evolution of anurans.     

Molecular cloning of natriuretic peptides from the heart of reptiles: loss of ANP in diapsid reptiles and birds

Atrial natriuretic peptide (ANP) and B-type NP (BNP) are hormones involved in homeostatic control of body fluid and cardiovascular regulation. Both ANP and BNP have been cloned from the heart of mammals, amphibians, and teleost fishes, while an additional cardiac peptide, ventricular NP, has been found in selected species of teleost fish. However, in chicken, BNP is the primary cardiac peptide identified thus far. In contrast, the types of NP/s present in the reptilian heart are unknown, representing a considerable gap in our understanding of NP evolution. In the present study, we cloned and sequenced a BNP cDNA from the atria of representative species of reptile, including crocodile, lizard, snake, and tortoise. In addition, we cloned BNP from the pigeon atria. The reptilian and pigeon BNP cDNAs had ATTTA repeats in the 3' untranslated region, as observed in all vertebrate BNP mRNAs. A high sequence homology was evident when comparing reptile and pigeon preproBNP with the previously identified chicken preproBNP. In particular, the predicted mature BNP-29 was identical between crocodile, tortoise, and chicken, with pigeon having a single amino acid substitution; lizard and snake BNP had seven and nine substitutions, respectively. Furthermore, an ANP cDNA could only be cloned from the tortoise atria. Since ANP was not isolated from the heart of any non-chelonian reptile and appears to be absent in birds, we propose that the ANP gene has been lost after branching of the turtles in the amniote line. This data provides new avenues for research on NP function in reptiles.     

Ambient salinity-dependent effects of homologous natriuretic peptides (ANP,VNP, and CNP) on plasma cortisol level in the eel

The effects of three eel natriuretic peptides (NPs), i.e., ANP, VNP, and CNP on plasma cortisol levels were investigated in conscious freshwater (FW)- and seawater (SW)-adapted eels with permanent arterial catheter. The experiment was performed between 9:00 and 15:00 of the day, when the natural plasma cortisol level was relatively stable. After a single intra-arterial injection of ANP, VNP, or CNP at 100 pmol/kg, only CNP, but not ANP or VNP, increased plasma cortisol concentration in FW eels. In SW eels, however, only ANP at the same dose increased plasma cortisol concentration. The effect of CNP in FW eels and that of ANP in SW eels were dose-dependent between 10 and 1000 pmol/kg. On the other hand, ANP and VNP were equally effective, but CNP was ineffective, in increasing hematocrit in both FW and SW eels. These results show that the effect of NPs on plasma cortisol level is dependent on the ambient salinity in the eel. Since cortisol plays a pivotal role in environmental adaptation of fishes, the results suggest a possible involvement of ANP and CNP in the adaptation to SW and FW, respectively. Furthermore, this is the first evidence showing that ANP and VNP exert different effects in fish despite they share the same receptor, NPR-A.     

快速测定脑利钠肽预测充血性心力衰竭患者预后的价值

目的　探讨快速测定脑利钠肽预测充血性心力衰竭近期预后的价值。方法　 70例充血性心力衰竭住院患者 ,NYHA心功能Ⅲ级 3 7例、Ⅳ级 3 3例。入院时、出院前或临终前 2 4小时内分别测定血浆BNP ,分析住院治疗前后BNP水平变化与心源性死亡、3 0天内再住院事件的关系。结果　 2 3例患者出现终点事件 (因心功能恶化死亡 6例、再住院 17例 ) ,其入院时BNP水平 ( 15 16pg/ml± 872pg/ml)高于未发生临床终点者 ( 10 3 7pg/ml± 65 4pg/ml) ,P <0 .0 1;发生临床终点者住院期间BNP升高 3 18pg/ml ,而未发生终点事件的患者 ,住院期间BNP平均降低 3 5 9pg/ml ,P <0 .0 1;BNP升高组患者发生临床终点 68.2 % ,BNP降低组患者发生临床终点 16.7% ,P <0 .0 0 5。结论　BNP水平可预测失代偿充血性心力衰竭患者的近期预后     

Genetic polymorphism of the type A human natriuretic peptide receptor (NPR-A) gene contributes to the interindividual variability in the BNP system

AIMS: To analyse the contribution of recently described genetic polymorphisms in the human natriuretic peptide receptor (NPR-A) to the interindividual variability in the BNP system. METHODS AND RESULTS: We evaluated NT-proBNP in 402 subjects, including healthy controls (n=93), patients with acute coronary syndrome (n=194) and heart failure (n=115). Three polymorphic sites encoding six common haplotypes of the NPR-A receptor gene, including three haplotypes in the 5' region (CT11, CT10 and CT6) and three haplotypes in the 3' region (3-plus, 4-minus and 4-plus), were studied. The frequency of the identified "4-minus" haplotype was higher in control subjects with high NT-proBNP (>75th percentile) levels as compared to those with low NT-proBNP levels (15.2% vs. 5.7%, p<0.05). In the control subjects, carriers of the "4-plus/4-minus" genotype had about 2-fold higher median NT-proBNP levels than individuals with other genetic variants (142 pg/ml (88-371 pg/ml) vs. 71 pg/ml (35-111 pg/ml, p=0.011). In contrast, in patients with cardiovascular disorders no relation between NT-proBNP and the described polymorphisms was observed. CONCLUSION: The "4-minus" haplotype of the NPR-A receptor gene is associated with high NT-proBNP values and is a genetic determinant of the interindividual variability in the BNP system in healthy individuals but probably not in patients with cardiovascular disorders.     

Salinity-dependent in vitro effects of homologous natriuretic peptides on the pituitary-interrenal axis in eels

We examined the effects of atrial, B-type, ventricular and C-type natriuretic peptides (ANP, BNP, VNP and CNP1, 3, 4) on cortisol secretion from interrenal tissue in vitro in both freshwater (FW) and seawater (SW)-acclimated eels. We first localized the interrenal and chromaffin cells in the eel head kidney using cell specific markers (cholesterol side-chain cleavage enzyme (P450ssc) and tyrosine hydroxylase (TH), respectively) and established the in vitro incubation system for eel interrenal tissue. Unexpectedly, none of the NPs given alone to the interrenal tissue of FW and SW eels stimulated cortisol secretion. However, ANP and VNP, but not BNP and three CNPs, enhanced the steroidogenic action of ACTH in SW interrenal preparations, while CNP1 and CNP4, but not ANP, BNP, VNP and CNP3, potentiated the ACTH action in FW preparations. These salinity dependent effects of NPs are consistent with the previous in vivo study in the eel where endogenous ACTH can act with the injected NPs. 8-Br-cGMP also enhanced the ACTH action in both FW and SW eel preparations, suggesting that the NP actions were mediated by the guanylyl cyclase-coupled NP receptors (GC-A and B) that were localized in the eel interrenal. Further, ANP and CNP1 stimulated ACTH secretion from isolated pituitary glands of SW and/or FW eels. In summary, the present study revealed complex mechanisms of NP action on corticosteroidogenesis through the pituitary-interrenal axis in eels, thereby providing a deeper insight into the role of the NP family in the acclimation of this euryhaline teleost to diverse salinity environments.     

Four natriuretic peptides (ANP, BNP, VNP and CNP) coexist in the sturgeon: identification of BNP in fish lineage

The natriuretic peptide (NP) family is composed of three members: atrial, brain/ventricular and C-type NPs (ANP, BNP/VNP and CNP respectively) in tetrapods and teleostean fish, but only CNP in elasmobranch fish. In order to trace the process of divergence of the NP family in early vertebrate evolution, we attempted to detect NPs in the primitive ray-finned fish, the sturgeon (Acipenser transmontanus). Unexpectedly, we isolated four distinct NP cDNAs from the heart and brain of this chondrostean fish. The single NP from the brain was CNP, as judged from the lack of C-terminal 'tail' sequence extending from the intramolecular ring. Two of the three cardiac NPs were ANP and VNP, as judged by the presence of an amidation signal at its C-terminus (ANP) and a long and conserved C-terminal tail sequence (VNP) respectively. The third cardiac NP was most probably BNP because it possessed all the features characteristic of BNP including: (1) the presence of dibasic amino acids within the intramolecular ring; (2) the presence of AUUUA repeats in the 3'-untranslated region of its mRNA; (3) equivalent expression of its mRNA in the atrium and ventricle and appreciable expression in the brain. Based on the sturgeon BNP sequence, we further isolated BNP cDNA from the heart of tilapia and pufferfish for the first time in teleostean fish. Phylogenetic analysis of the precursors showed that newly identified NPs belong to each group of the four NPs. The current identification of both VNP and BNP in the sturgeon clearly showed that BNP and VNP are coded by distinct genes, and that the NP family consists of at least four members in the ray-finned fish. VNP has not been molecularly identified in mammals but its presence is suggested from physiological studies; heterologous fish VNP exhibited more potent vasorelaxant activity than homologous mammalian ANP in the isolated coronary artery of dogs.     

What is the most cost-effective strategy to screen for left ventricular systolic dysfunction: natriuretic peptides, the electrocardiogram, hand-held echocardiography, traditional echocardiography, or their combination?

AIMS: To assess the screening characteristics and cost-effectiveness of screening for left ventricular systolic dysfunction (LVSD) in community subjects. METHODS AND RESULTS: A total of 1392 members of the general public and 928 higher risk subjects were randomly selected from seven community practices. Attending subjects underwent an ECG, N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels, and traditional echocardiography (TE). A total of 533 consecutive subjects underwent hand-held echocardiography (HE). The screening characteristics and cost-effectiveness (cost per case of LVSD diagnosed) of eight strategies to predict LVSD (LVSD <45% on TE) were compared. A total of 1205 subjects attended. Ninety six per cent of subjects with LVSD in the general population had identifiable risk factors. All screening strategies gave excellent negative predictive value. Screening high-risk subjects was most cost-effective, screening low-risk subjects least cost-effective. TE screening was the least cost-effective strategy. NTproBNP screening gave similar cost savings to ECG screening; HE screening greater cost-savings, and HE screening following NTproBNP or ECG pre-screening the greatest cost-savings, costing approximately 650 Euros per case of LVSD diagnosed in high-risk subjects (63% cost-savings vs.TE). CONCLUSION: Thus several different modalities allow cost-effective community-based screening for LVSD, especially in high-risk subjects. Such programmes would be cost-effective and miss few cases of LVSD in the community.     

Effects of angiotensin II and natriuretic peptides of the eel on prolactin and growth hormone release in the tilapia,Oreochromis mossambicus

The effects of angiotensin II (ANG II) and natriuretic peptides (NPs) of the eel (ANP, atrial natriuretic peptide; CNP, C-type natriuretic peptide; and VNP, ventricular natriuretic peptide) on prolactin (PRL(188) and PRL(177)) and growth hormone (GH) release from the organ-cultured tilapia pituitary were examined. Eel ANG II at concentrations greater than 1 nM stimulated the release of PRL(188) and PRL(177) in a dose-related manner during the first hour of incubation. Significant stimulation by 100 nM ANG II on PRL(177) release was observed until 4h of incubation, and on PRL(188) release until 12 h. No effect of ANG II was seen on GH release. None of the NPs altered the release of PRLs at any time point. On the other hand, eel VNP at concentrations greater than 1 nM stimulated GH release in a dose-related manner after 4 h, and significant stimulation was observed until 48 h. Eel CNP was less effective than eel VNP; significant stimulation of GH release was observed at 1 and 10 nM during 24-48 h of incubation. No significant effect of eel ANP on GH release was seen at any concentration. ANG II had no effect on GH release at any time point. There was no change in mRNA levels of PRLs or GH in the pituitaries incubated with ANG II for 8 h or those incubated with the NPs for 48 h. These results indicate rapid and short-lasting stimulation by ANG II on PRL release and slow and long-lasting stimulation by VNP and CNP on GH release from the tilapia pituitary.     

Expression of natriuretic peptides, nitric oxide synthase, and guanylate cyclase activity in frog mesonephros during the annual cycle

Natriuretic peptides (NPs), a family of structurally related hormones and nitric oxide (NO), generated by nitric oxide synthase (NOS), are believed to be involved in the regulation of fluid balance and sodium homeostasis. Differential expression and regulation of these factors depend on both physiological and pathological conditions. Both NPs and NO act in target organs through the activation of guanylate cyclase (GC) and the generation of guanosine 3',5'-cyclic monophosphate (cGMP), which is considered a common messenger for the action of these factors. The present study was designed to investigate--by histochemical methods--the expression of some NPs (proANP and ANP) and isoforms of NOS (neuronal NOS, nNOS, and inducible NOS, iNOS) in the mesonephros of Rana esculenta in different periods of the year including hibernation, to evaluate possible seasonal changes in their expression. We also studied the enzyme activity of NOS-related nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) and of GC. The experiments were performed on pieces of kidney of R. esculenta collected in their natural environment during active and hibernating life. The study was carried out using immunohistochemical techniques to demonstrate proANP, ANP, and some NOS isoforms. Antigen capture by enzyme linked immunosorbent assay (ELISA) was also performed to determine the presence of NPs in the frog kidney extract. Enzyme histochemistry was used to demonstrate the NOS-related NADPHd activity at light microscopy; GC activity was visualized at the electron microscope, using cerium as capture agent. The application of the immunohistochemical techniques demonstrated that frog mesonephros tubules express different patterns of distribution and/or expression of ANP and NOS during the annual cycle. Comparing the results obtained on active and hibernating frogs has provided interesting data; the NOS/NADPHd and GC activities showed some variations as well. Furthermore, the presence of NPs in the frog kidney extract was evidenced by dose-dependent response in the ELISA. The data suggest that both ANP and NO are intra-renal paracrine and/or autocrine factors which may modulate the adaptations of frog renal functions to seasonal changes through the action of the cGMP generated from GC activity.     

Comparison of treatment effects of bevantolol and metoprolol on cardiac function and natriuretic peptides in patients with dilated cardiomyopathy

 This study was designed to compare the efficacy of bevantolol, a β₁-selective blocker with α-blockade and vasodilating activity, with that of metoprolol, a β₁-selective receptor blocker, for the treatment of idiopathic dilated cardiomyopathy (DCM). Forty-one patients with DCM were enrolled to receive either bevantolol or metoprolol in addition to the standard therapy for DCM. They were classified into two groups: 16 patients were treated with bevantolol and 25 were treated with metoprolol. Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured before treatment and after 6 months of treatment. Left ventricular dimension at end-diastole and end-systole was significantly lower and fractional shortening was significantly higher after treatment than before treatment in both groups. The plasma ANP and BNP levels were significantly decreased in both groups. Changes in all variables, except for systolic blood pressure, showed no significant differences between the two groups. In conclusion, bevantolol showed parallel beneficial effects to those of metoprolol on cardiac function and natriuretic peptides in patients with DCM. Received: May 10, 2002 / Accepted: August 13, 2002 Correspondence to Y. Hara     

脑利钠肽和C反应蛋白及左心室舒张功能与老年血液透析患者心脑血管事件的相关性研究

目的 观察脑利钠肽(BNP)和C反应蛋白(CRP)水平及应用组织多普勒超声心动图测定患者静息状态心室舒张早期二尖瓣血流速度(E)与二尖瓣环运动速度(Em)的比值(E/Em)与老年血液透析患者的心脑血管事件(CVD)风险的相关性. 方法 2006年1月至2011年6月,对96例老年血液透析患者进行前瞻性队列研究,每月随访1次,随访时间24～30个月,根据是否发生CVD事件分为CVD组(35例)和对照组(61例).记录观察开始时患者临床和实验室资料及超声心动图结果,记录患者因CVD事件住院和死亡的原因和时间. 结果 CVD组CRP、BNP水平[分别为(3.1±6.7)mg/L、(1345.2±1427.8)pmol/L]较对照组[分别为(1.8±1.2)mg/L、(719.8±1073.8)pmol/L]升高,差异有统计学意义(t值分别为2.14、-2.82,P＜0.05和P＜0.01);E/Em升高(t=5.229,P＜0.01).Kaplan-Meier生存曲线结果显示,BNP≥500 pmol/L、CRP≥1.5 mg/L、E/Em≥17时,老年血液透析患者的CVD发生率升高(P＜0.05或P＜0.01).Cox回归模型提示,CRP≥1.5 mg/L,BNP≥500 pmol/L和E/Em≥17为老年血液透析患者CVD独立危险因素.Bivariate 相关分析结果显示,LogBNP水平与E/Em值呈线性相关(r=0.23,P＜0.05). 结论 BNP、CRP 、及E/Em升高与老年血液透析患者CVD发生率相关.     

Levosimendan-induced reduction in natriuretic peptide levels during the treatment of decompensated heart failure: Clinical implications — Reply

Although, the potential use of natriuretic peptide testing in treatment monitoring of heart failure remains to be fully clarified, levosimendan-induced reduction in natriuretic peptide levels has consistently been reported to be associated with favorable clinical, hemodynamic, anti-inflammatory and anti-apoptotic effects. Several studies demonstrated that not only is plasma natriuretic peptide level important predictor of long-term outcomes, but changes in natriuretic peptide levels during the treatment of heart failure are also associated with corresponding changes in morbidity and mortality. Re-analysis of the data from our previously published study suggested a greater percentage of NT-proBNP reduction at 48 h in patients who survived compared to those who died in both levosimendan (− 36 ± 8% vs − 24 ± 13%, respectively) and dobutamine (− 32 ± 8% vs + 9 ± 32%, respectively) treatment groups, although not statistically different. The changes in natriuretic peptide levels during therapy reflect short-term hemodynamic improvements and effectiveness of drug regimens, but also may have a role in predicting long-term outcomes.     

慢性心力衰竭患者血钠水平与血浆肾素活性、抗利尿激素、脑利钠肽的关系

目的探讨慢性心力衰竭(心衰)患者血钠水平与血浆肾素活性(PRA)、抗利尿激素(ADH)、脑利钠肽(BNP)的关系。方法用放射免疫法测定41例伴低钠血症的心衰患者(低血钠组)和35例正常血钠的慢性心衰患者(正常血钠组)的血浆 PRA、ADH、BNP 水平并观察两组患者3个月内的再住院率。结果低血钠组的心衰患者血浆 PRA、ADH、BNP 水平均较正常血钠组相同心功能级别者显著升高。低血钠组与正常血钠组心功能Ⅱ级、Ⅲ级、Ⅳ级的比较:PRA(单位:ng·ml~(-1)·h~(-1))分别为2.7±1.0与1.8±0.7、4.3±1.2与3.0±0.9、5.6±1.3与3.5±1.1,P<0.05,ADH(单位:ng/L)分别为59.7±17.4与48.6±15.3、68.4±17.6与56.3±19.2、75.3±20.0与51.4±16.2,P<0.05,BNP(单位:ng/L)分别为276.4±75.2与185.3±55.3、380.1±113.6与258.5±62.1、564.0±125.2与405.3±102.9,P<0.05;血浆 PRA、ADH、BNP 与血钠呈显著负相关(分别为 r=-0.31、P<0.05,r=-0.28、P<0.05,r=-0.80、P<0.01);低血钠组再住院率增高。结论低钠血症可能促进慢性心衰患者血浆 PRA、ADH、BNP 分泌增加,心衰伴低钠血症患者的神经内分泌水平激活更明显。     

老年人心力衰竭与C-反应蛋白肾上腺髓质素脑钠素和基质金属蛋白酶的关系

目的研究老年充血性心力衰竭(CHF)患者血浆中高敏C-反应蛋白(hs-CRP)、肾上腺髓质素(ADM)、脑钠素(BNP)和基质金属蛋白酶(MMPs)的水平,与心力衰竭的严重程度、左室射血分数(LVEF)的关系及各指标的相互关系。方法采取50例CHF患者和24例健康对照者空腹静脉血,测定hs-CRP、ADM、BNP、MMP-2、MMP-9水平,用彩色超声探测仪测定LVEF。CHF组按美国纽约心脏病学会(NYHA)心功能分级标准分为Ⅱ、Ⅲ、Ⅳ级组。结果CHF组hs-CRP、ADM、BNP、MMP-2、MMP-9和LVEF水平〔分别为(7.7±4.4)mg/L、(34.9±9.4)ng/L、(154.5±59.7)ng/L、(149.9±60.3)μg/L(、182.0±57.2)μg/L(、32.4±5.0)%〕与对照组〔分别为(0.9±0.7)mg/L、(16.3±2.7)ng/L(、38.8±11.4)ng/L、(149.9±60.3)μg/L、(70.1±6.8)μg/L、(58.4±3.1)%〕比较,差异有统计学意义(均为P<0.01);CHF组hs-CRP、ADM、BNP、MMP-2、MMP-9浓度与LVEF均呈显著负相关(均为P<0.01),且hs-CRP、MMP-2、MMP-9浓度与LVEF负相关更显著。CHF组hs-CRP、ADM、BNP、MMP-2、MMP-9相互间呈显著的正相关(P<0.01),且hs-CRP与MMP-2、MMP-9间的相关性(r为0.77、0.82)较hs-CRP与ADM、BNP间的相关性(r为0.49、0.51)更显著。结论hs-CRP、ADM、BNP、MMP-2、MMP-9共同参与老年人CHF的发生和发展过程;hs-CRP与MMP-2、MMP-9能更准确反映左室功能障碍程度;MMPS在老年人CHF心室的重塑中具有重要的作用。     

Plasma N-terminal pro-brain natriuretic peptide concentration predicts coronary events in men at work: a report from the BELSTRESS study.

AIMS: Increased levels of neurohormonal markers, including the N-terminal fragment of pro-brain natriuretic peptide (NT-pro-BNP), have been shown to be of prognostic significance in patients with heart failure or coronary heart disease (CHD). The aim of this study was to study the predictive value of NT-pro-BNP for coronary events in a middle-aged population of men at work. METHODS AND RESULTS: A nested case-control study was performed in a large cohort of over 10 000 men at work (aged 35-59) after a median follow-up of 2.66 years. In total, 66 individuals who developed coronary events were matched on a 3-to-1 basis to 198 controls free of coronary events during follow-up. Besides clinical characteristics and conventional cardiac risk factors, NT-pro-BNP (electrochemiluminiscence assay, Roche diagnostics) and serum creatinine levels were determined. In univariable analysis, cases were more frequently current smokers and diabetics, had more frequently a history of CHD, and had higher levels of total cholesterol and systolic blood pressure (SBP), and lower levels of HDL cholesterol. A highly significant difference (P < 0.0001) was noted for NT-pro-BNP levels between cases (median 48.5 pg/mL, interquartile range 26.4-116.6 pg/mL) and controls (30.0 pg/mL, 19.5-47.6 pg/mL). In multivariable conditional logistic regression analysis, NT-pro-BNP remained strongly associated with risk for coronary events [third vs. first tertile, odds ratio (95% CI) 3.24 (1.18-8.85)], independent of body mass index, smoking, diabetes, SBP, total and HDL cholesterol, creatinine, and previous CHD. CONCLUSION: NT-pro-BNP is a strong predictor of coronary events in men at work after a relatively short period, even after adjustment for conventional risk factors.