鼠股动脉神经肽Y受体亚型的定性分析

目的了解神经肽Ｙ（ＮＰＹ）受体亚型在鼠股动脉中膜层的分布情况。方法对鼠股动脉中膜层进行ＮＰＹ受体亚型放射自显影分析。结果ＮＰＹ受体亚型Ｙ１、Ｙ２共存于鼠股动脉中膜层，Ｙ１受体亚型密度高于Ｙ２受体亚型。结论ＮＰＹ可能通过Ｙ１、Ｙ２受体亚型共同完成缩血管作用，参与高血压的发病机制。     

心血管紧张素-（1-7）在心血管系统中的作用

血管紧张素-（1-7）是肾素-血管紧张素系统中具有重要生物学作用的终末活性产物,可通过直接作用于心血管中枢调节心血管活动以及与心脏和血管上特异性受体结合而发挥改善心功能、降低血压、抑制心脏和血管重构作用。现就血管紧张素-（1—7）对心血管系统中的作用综述如下。     

血管紧张素-(1-7)在心血管系统中的作用

血管紧张素-(1-7)是肾素-血管紧张素系统中具有重要生物学作用的终末活性产物,可通过直接作用于心血管中枢调节心血管活动以及与心脏和血管上特异性受体结合而发挥改善心功能、降低血压、抑制心脏和血管重构作用.现就血管紧张素-(1-7)对心血管系统中的作用综述如下.     

甲状腺激素对心血管系统影响的新认识

甲状腺激素与心血管系统关系密切,甲状腺激素不仅可以作用于甲状腺激素受体,而且可以影响肾上腺素能受体和胆碱能受体的功能,并调节腺苷酸环化酶、钠—钾ATP酶、钙转运及心脏肌球蛋白ATP同工酶等活性,对心血管系统产生直接的或间接的作用。不管是显性甲状腺疾病、亚临床甲状腺疾病还是甲状腺激素抵抗,都常伴有心血管血液动力学改变的症状和体征,并可出现二尖瓣脱垂、心率变异的改变以及肾素—血管紧张素系统的异常等。另一方面,心血管疾病患者也可出现甲状腺激素代谢的变化。     

人尾加压素的生物效应研究

1996年首次从人体中克隆出尾加压素－Ⅱ，G蛋白耦联受体－GPR14是尾加压素－Ⅱ的特异性受体，主要分布于血管平滑肌，内皮，心肌以及冠状动脉粥样硬化的病变部位。尾加压素－Ⅱ兼有缩，舒血管及较强的心 肌收缩作用，其中缩血管作用最为显著，在心血管稳态调节中起重要作用。     

尾加压素Ⅱ与血管重塑

尾加压素Ⅱ(urotensinⅡ,UⅡ)是继内皮素之后在哺乳动物体内新发现的缩血管活性肽,其特异性受体为GPR14(UT),广泛分布于人类心血管系统,包括血管平滑肌、内皮和血管外膜以及心肌细胞和心肌成纤维细胞等。在某些病理状态下如粥样硬化斑块、新生内膜等表达上调,表明UⅡ在心血管系统疾病的发生发展中发挥着重要作用。现将UⅡ与血管重塑的关系作简要综述。     

肾上腺髓质素对心血管系统保护作用机制的研究进展

肾上腺髓质素是1993年由日本学者K itamura等从人的嗜铬细胞瘤组织中发现并分离的一种心血管活性多肽,具有多种生物学活性,广泛分布于全身各系统。其中心血管组织是肾上腺髓质素的重要来源,肾上腺髓质素以自分泌/旁分泌方式抑制心肌细胞及血管内皮细胞凋亡,抗氧化应激,抑制心血管系统重塑及影响血流动力学等发挥对心血管的保护作用,是一种重要的器官保护因子。活性肾上腺髓质素由其前体裂解而成,作用于降钙素基因相关肽(CGRP)受体和肾上腺髓质素特异性受体,引起受体活化后通过多种信号转导通路实现其功能。     

尾加压素Ⅱ与血管重塑

尾加压素Ⅱ(urotensinⅡ,UⅡ)是继内皮素之后在哺乳动物体内新发现的缩血管活性肽,其特异性受体为GPR14(UT),广泛分布于人类心血管系统,包括血管平滑肌、内皮和血管外膜以及心肌细胞和心肌成纤维细胞等。在某些病理状态下如粥样硬化斑块、新生内膜等表达上调,表明UⅡ在心血管系统疾病的发生发展中发挥着重要作用。现将UⅡ与血管重塑的关系作简要综述。     

内皮素与肝硬化

内皮素是一类具有广泛生物学作用的活性肽，可通过与受体结合后发挥其生物学效应，主要生理功能是缩血管和升压作用，近年研究表明，肝脏存在大量的内皮素受体，内皮素可引起肝脏缺血缺氧，门静压力升高；内皮素还与肝硬化腹水的形成，侧支循环的建立有重要关系。     

血透患者血浆神经肽Y,神经降压素与心肌肥厚关系

血透患者血浆神经肽Ｙ、神经降压素与心肌肥厚关系张建国朱妙珍李天星何亚妮关键词血液透析左心室肥厚血管活性肽目前神经肽Ｙ（ＮＰＹ）和神经降压素（ＮＴ）对心血管系统的重要调控作用已有较深入研究［１］，而其在慢性肾衰（ＣＲＦ）左心室肥厚（ＬＶＨ）中的研究鲜有...     

Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPY Y5 receptors

Neuropeptide Y (NPY) has been shown to participate in the cardiovascular response mediated by the sympathetic system. In this report, we investigate the growth factor properties of NPY on cardiac myocytes. Mitogen-activated protein kinases (MAPK) are key signaling molecules in the transduction of trophic signals. Therefore, the role of NPY in inducing MAPK activation was studied in mouse neonatal cardiomyocytes. Exposure of neonatal cardiomyocytes to either NPY, phenylephrine, or angiotensin II induces a rapid phosphorylation of the extracellular responsive kinase, the c-jun N-terminal kinase, and the p38 kinase as well as an activation of protein kinase C (PKC). Moreover, NPY potentiates phenylephrine-induced MAPK and PKC stimulation. In contrast, NPY has no synergistic effect on angiotensin II-stimulated MAPK phosphorylation or PKC activity. NPY effects are pertussis toxin-sensitive and calcium-independent and are mediated by NPY Y5 receptors. Taken together, these results suggest that NPY, via G(i) protein-coupled NPY Y5 receptors, could participate in the development of cardiac hypertrophy during chronic sympathetic stimulation by potentiating alpha-adrenergic signals.     

Centtral Interactions Between Noradrenaline and Neuropeptide Y in the Rat: Implications for Blood Pressure Control

Neuropeptide Y (NPY) and noradrenaline are co-localised in central neurones and both transmitters exert cardiovascular effects. Using microdialysis and push-pull techniques to measure transmitter release in vivo and microinjection studies, we examined the role(s) of central noradrenaline and NPY in blood pressure regulation in the hypothalamus and nucleus tractus solitarius (NTS) of the rat. Hypothalamic noradrenaline release was increased following haemorrhage and reduced after phenylephrine infusion. Ageing is associated with markedly reduced NPY concentrations in the hypothalamus. 18-month old animals showed a reduced ability to release both NPY and noradrenaline to a potassium depolarisation stimulus. NTS administration of NPY induced dose-dependent decreases in blood pressure and heart rate. The depressor but not the bradycardic response was attenuated by prior administration of yohimbine. NTS microinjection of 23 pmol NPY induced similar cardiovascular effects in spontaneously hypertensive and Wistar Kyoto rats. NPY and noradrenaline appear to interact at several sites in the brain known to be important for blood pressure control.     

Neuropeptide Y and gamma-melanocyte stimulating hormone (γ-MSH) share a common pressor mechanism of action

Central circuits known to regulate food intake and energy expenditure also affect central cardiovascular regulation. For example, both the melanocortin and neuropeptide Y (NPY) peptide families, known to regulate food intake, also produce central hypertensive effects. Members of both families share a similar C-terminal amino acid residue sequence, RF(Y) amide, a sequence distinct from that required for melanocortin receptor binding. A recently delineated family of RFamide receptors recognizes both of these C-terminal motifs. We now present evidence that an antagonist with Y1 and RFamide receptor activity, BIBO3304, will attenuate the central cardiovascular effects of both gamma-melanocyte stimulating hormone (γ-MSH) and NPY. The use of synthetic melanocortin and NPY peptide analogs excluded an interaction with melanocortin or Y family receptors. We suggest that the anatomical convergence of NPY and melanocortin neurons on cardiovascular control centers may have pathophysiological implications through a common or similar RFamide receptor(s), much as they converge on other nuclei to coordinately control energy homeostasis. K. A. Gruber—on leave from Department of Biological Sciences, California State Polytechnic University, Pomona, CA, USA.     

心血管调节肽与先天性心脏病肺动脉高压相关关系的研究

目的本文研究两种心血管调节肽--神经肽Y(NPY)、降钙素基因相关肽(CGRP)和肿瘤坏死因子(TNF)与先天性心脏病(先心病)肺动脉高压(肺高压)的关系;并检测血清CGRP、NPY浓度作相关分析,以判断它们是否具有相关性.方法采用放射免疫法测定80例先心病患儿[13例为非肺高压组,67例为肺高压组(同时根据肺高压的程度又分为轻、中、重度患儿)]血清NPY、CGRP及TNF浓度,将2组进行比较,应用统计学方法进行方差分析,t检验.结果非肺高压组与肺高压组轻、中、重度患儿血清NPY及CGRP浓度均存在显著性差异(P＜0.01).手术前后肺高压组轻、中度患儿NPY和CGRP浓度存在显著性差异(P＜0.01),而肺高压组重度者差异不明显;肺高压组外周血NPY与CGRP浓度存在负相关关系.结论3种活性物质在先心病肺高压的发生机制中有重要的作用,NPY/CGRP值的升高参与和促进了肺高压的形成和发展.     

Forearm blood flow responses to neuropeptide Y, noradrenaline and adenosine 5'-triphosphate in hypertensive and normotensive subjects

Neuropeptide Y (NPY), noradrenaline (NA) and adenosine 5'-triphosphate (ATP) are important co-transmitters in the sympathetic nervous system, which has a central role in cardiovascular control. In order to evaluate if hypertension is associated with alterations in vascular responses to sympathetic co-transmitters we studied the effects of intra-arterial infusion of NPY, NA and ATP on forearm blood flow. Blood flow was measured by venous occlusion plethysmography in six hypertensive (mean arterial blood pressure (MAP) 113 +/- 4 mmHg) and six matched normotensive subjects (MAP 97 +/- 3 mmHg). NPY and NA significantly reduced forearm blood flow, while a powerful increase was seen with ATP. Forearm vascular resistance, calculated as MAP divided by forearm blood flow, was significantly increased by NPY and NA and strongly reduced by ATP. There was no difference between hypertensive and normotensive subjects in response to either transmitter. In conclusion, vascular reactivity to intra-arterial administration of NPY, NA and ATP seems to be intact in hypertensive patients without metabolic aberrations.     

Enhanced endothelium-dependent vasodilation in subjects with Proline7 substitution in the signal peptide of neuropeptide Y

Neuropeptide Y (NPY) is a molecule that may have both vasoconstrictive and vasodilatory actions. A common polymorphism in the human NPY gene that results in the Leucine7 to Proline7 substitution (Leu7Pro) in the signal peptide part of the NPY was recently identified. This substitution has been associated with elevated serum cholesterol levels and with slightly accelerated progression rate of carotid intima-media thickness, thus suggesting increased risk of atherosclerosis in carriers of Pro7 substitution. Recent data also indicate that subjects with Pro7 substitution may have increased endothelial release of NPY. This study was undertaken to elucidate the effects of Leu7Pro polymorphism on arterial endothelial function. We measured flow-mediated endothelial-dependent dilatation (FMD) of the brachial artery in two separate populations: in 152 middle-aged men and in 95 prepubertal children. In both study populations, subjects with Pro7 substitution had 48-52% higher FMD compared with subjects having the wildtype (Leu7/Leu7) signal peptide sequence. We conclude that Pro7 substitution in signal peptide of the NPY is associated with enhanced endothelial-dependent vasodilation. Prospective studies are needed to determine whether Pro7 substitution is associated with increased or decreased risk of cardiovascular morbidity and mortality.     

Neuropeptide Y,left ventricular mass and function in patients with end stage renal disease

OBJECTIVE: Neuropeptide Y (NPY) is released during sympathetic stimulation and mediates the central effects of the adipostatic hormone leptin. The plasma concentration of NPY and leptin is increased in patients with end stage renal disease (ESRD), but it is unknown whether these substances are related to biochemical markers of sympathetic activity and to alterations in left ventricular (LV) mass and function in these patients. DESIGN: We investigated the relationship between NPY, norepinephrine (NE), leptin and echocardiographic measurements in a cross-sectional study in 198 patients with ESRD. RESULTS: NPY was directly related to plasma NE and heart rate but it was largely independent of arterial pressure and of retention of metabolic waste products. NPY was significantly higher in patients with LV hypertrophy and in those with LV systolic dysfunction than in those without these alterations. Of note, NPY emerged as an independent correlate of LV mass index and of LV ejection fraction (LVEF) (both P 相似文献   

Attenuation of long-lasting effects of sympathetic stimulation after repeated stimulation

Neuropeptide Y (NPY) is stored with norepinephrine in sympathetic nerves throughout the cardiovascular system and is released during activation of the sympathetic nervous system in humans and other animals. After stimulation of the cardiac sympathetic nerves in anesthetized dogs, the action of the vagus nerve on heart rate is attenuated for a prolonged period. This attenuation of cardiac vagal action is also seen after injection of NPY. Both sympathetic stimulation and exogenous NPY inhibit cardiac vagal effects by acting on postganglionic vagal nerves. Because the supply of neuropeptides to nerve terminals is by axonal transport, it might be expected that repeated stimulation of cardiac sympathetic nerves would deplete the sympathetic neural factor, proposed to be NPY. In all 11 dogs of this study, repeated episodes of stimulating the cardiac sympathetic nerve (16 Hz for 1 minute each) had a diminishing effect in attenuating cardiac vagal action. However, the episodes of sympathetic stimulation did not show diminishing effectiveness in increasing heart rate. Exogenous NPY had similar inhibitory effects on vagal action whether given at the beginning or the end of the episodes of sympathetic stimulation. Transmural stimulation of sympathetic nerves around rabbit ear arteries produced effects that are also mimicked by NPY. These are prolonged potentiation of contractions evoked by injection of norepinephrine or by brief bursts of transmural stimulation. Repeated stimulations in this case also had diminishing abilities to evoke such potentiations. Both sets of observations are consistent with repeated stimulation of sympathetic nerves causing depletion of a nonadrenergic transmitter, possibly NPY.     

Association analysis of the polymorphism T1128C in the signal peptide of neuropeptide Y in a Swedish hypertensive population

OBJECTIVE: The neuropeptide Y (NPY) signal peptide polymorphism T1128C has been linked to several risk factors for cardiovascular disease. The aim of the present study was to evaluate the significance of this polymorphism for cardiovascular and cerebrovascular disease outcome. DESIGN: In a prospective study cohort, 1032 hypertensive patients (174 myocardial infarction and 170 stroke patients and 688 matched controls) were analysed for the T1128C polymorphism in the NPY gene. METHODS: The dynamic allele specific hybridization (DASH) method was used for genotyping. Serum from the same participants was analysed for total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. RESULTS: The frequency of the NPY T1128C polymorphism was 8.4% among patients with a myocardial infarction or stroke, as compared to 5.1% in the control group (P = 0.040). The difference remained significant after adjustment for the cardiovascular risk factors age, sex, smoking status, body mass index, systolic and diastolic blood pressure, presence of diabetes, total cholesterol, HDL, LDL and triglycerides. CONCLUSIONS: The present study indicates that the NPY T1128C polymorphism is an independent predictor for myocardial infarction and stroke in a Swedish hypertensive population.     

Neuropeptide Y Y1 Receptor Antagonist (BIBP 3226) Attenuates Stress Evoked Tachycardia in Conscious Spontaneously Hypertensive Rats

The effects of a novel neuropeptide Y (NPY) Y1 receptor antagoniston resting mean blood pressure (MBP) and heart rate (HR) were observed inconscious spontaneously hypertensive rats (SHR). The interference of theantagonist with cardiovascular responses to mental stress andadministration of exogenous NPY were also investigated. SHR were randomlyreceived either the NPY Y1 receptor antagonist (BIBP 3226; n = 11)or its inactive enantiomer (BIBP 3435; n = 11) as an infusion (6mg/kg/h for 1.5 hours). Before, during, and after the infusion, rats were first stressed with a jet of air and then given a bolus injection of exogenous NPY (2 nmol/kg). There was no statistically significant difference of resting MBP and HR between the antagonist and enantiomer groups before, during, or after infusion. The stress-induced maximum increase in HR was significantly reduced during antagonist infusion (P <0.05). The effects of exogenous NPY on both MBP and HR were significantlyattenuated by antagonist infusion (P < 0.05, respectively), and theeffect lasted at least 1 hour after the end of the infusion. Plasmacatecholamine levels in response to stress were not significantly differentbetween the two groups. The results suggest that endogenous NPY Y1-receptormechanisms may be of minor importance in short-term regulation of MBP andHR in conscious adult SHR, but may be involved in the response to mentalstress.