雌激素在中枢肾素-血管紧张素系统功能异常诱导的高血压中的保护作用

雌激素主要由卵巢分泌,是一种类固醇激素。流行病学研究显示,绝经前女性的高血压发病率明显低于同龄男性。研究表明,雌激素可通过影响中枢肾素-血管紧张素系统(RAS)组分的功能发挥其在中枢血压调控中的保护作用。雌激素作用于雌激素受体可抑制RAS增压信号通路或/和激活其减压信号通路,衰减中枢核团内自主神经元兴奋性进而延缓外界刺激诱导的高血压的发生。本文通过对雌激素在中枢RAS活动增强诱导的高血压发生中心血管保护作用及作用机制等方面进行综述,为临床开展性别差异性的高血压防治提供新思路。     

红细胞抗高血压因子降压作用的进一步研究

我们曾报道原发性高血压患者(EHS)红细胞抗高血压因子(AHF)具有缓慢而持久的降压作用。本工作表明,AHF对卒中易感型自发性高血压大鼠(SHRsp)还具有快速短暂的降压作用,注射AHF后10—30s,SHRsp收缩压从原水平的26.8±1.7kPa降至20.1±1.5kPa(P<0.001)。正常人和大鼠红细胞AHF的降压作用明显强于EHS和高血压大鼠AHF。此外我们还发现EHS血浆中存在升压物质。以上结果提示,AHF缺乏和升压物质含量相对较高可能是原发性高血压发病的一个重要原因。     

缬沙坦抑制SHR心血管重构涉及降钙素基因相关肽的初步研究

缬沙坦是临床常用的抗高血压药物,除降压外其对心血管重构的作用也逐渐引起人们的重视.降钙素基因相关肽(calcitonin gene related peptide,CGRP)是目前已知的最强舒血管物质,也参与了心血管重构的过程.以缬沙坦治疗自发性高血压大鼠(spontaneously hypertensive rats,SHR)8周,能明显降低SHR血压,抑制心肌肥厚,改善心室重构,同时也显著抑制胸主动脉和肠系膜上动脉血管重构.缬沙坦治疗还显著升高SHR大鼠血浆CGRP浓度,上调背根神经节和肠系膜上动脉中CGRP表达.结果提示,缬沙坦降低SHR大鼠血压,改善心血管重构,其作用可能与提高CGRP水平有关.     

P物质对心血管系统的作用

P物质的生理作用,主要表现在神经系统和心血管系统二方面,前者已有专文讨论;后者在国内期刊还未见介绍。本文对P物质在心血管系统的作用做一简介。一、降血压1931年von Euler从牛脑和肠提取出一种未知物质,发现它能降低动物的血压。当动脉或静脉注入部分纯的P物质或P物质的纯品,都能引起短时间的血压降低。降压作用适用于禽类、所有哺乳动物和人。降压效用的高低因动物的种属而异,对兔和狗引起降压的P物质阈剂量比猫和老鼠低,通常3～5个单位的P物质就能使兔子降压20毫米汞柱。使猫达到该降压值则需要20～30单位,所以常用兔,特别是用狗作实验对象。P物质对猴和人也能降压。     

蛇毒中的降压成分研究进展

目前世界上已知的蛇类有3000余种,其中有毒蛇约占20%。蛇毒是一种由蛋白质、多肽等有机和无机小分子组成的复杂混合物,因其具有多种生化和药理活性,能广泛应用于各个领域。研究表明蛇毒对血压有一定影响,其降压机制主要有蛇毒抗凝血因子Ⅱ通过介导NO的释放降低血压,缓激肽增强肽主要通过抑制血管紧张素转换酶和增加内源性缓激肽的作用而发挥作用,利钠肽通过抑制肾素-血管紧张素和醛固酮系统调控血压,而磷脂酶A_2主要是促进游离脂肪酸(其中最重要的是花生四烯酸)和溶血磷脂的释放起到降低血压的作用。因此,明确蛇毒的降压成分以及作用机制与效果,对降压药物的开发以及高血压的治疗至关重要。     

高血压病人血浆中神经降压素含量的变化

神经降压素(NT)是由13个氨基酸组成的一种脑-肠肽,它具有扩张血管、降低血压及其他多种生理功能。但是,NT与人类高血压之间的关系,迄今尚未见报道。本研究测定了高血压病人血浆中的NT含量,为探讨NT在高血压中的临床意义提供实验依据。 正常对照组:12例(男性8例,女性4例),年龄20～47岁,经体检证明无脑血管病和高血压。高血压     

尖吻蝮蛇毒及其降压组分降压机制的探讨

用离子交换及凝胶过滤的方法,从尖吻蝮蛇毒中分离纯化出具有显著降压作用的组分,经聚丙烯酰胺凝胶圆盘电泳及等电聚焦电泳证实为单一区带,其等电点为６．８,分子量为３１０００,ＬＤ５０为７．３５±０．５１ｍｇ／ｋｇ（ｉ．ｖ小白鼠）。该组分能使兔和大白鼠颈动脉血压降低,其降压作用在一定的剂量范围内呈较明显的剂量依赖性,同时观察大白鼠肠系膜微循环微动脉管径的变化,发现大白鼠颈动脉血压降低与微动脉扩张有关。兔血液流变学实验表明该组分能加快红细胞电泳速度、降低全血及血浆粘度等,提示该降压组分的降压作用可能与其扩张微小血管及降低血液粘度有关。     

心房促尿钠排泄因子

心房促尿钠排泄因子是心腔产生的一种激素。哺乳类心房肌细胞,形态上有分泌作用的特性,能产生一种多肽激素。因这种激素有利尿和降压作用,还能抑制肾素、醛固酮的分泌,Bold(1981)将它看成是促尿钠排泄因子,其作用参与电解质及血压调节。系统发生早,据推论这种多肽不同功能与种类环境相一致。了     

神经营养因子NGF、BDNF与围绝经期妇女认知功能关系的研究进展

神经营养因子(NTFs)是近几年神经科学研究的热点,研究显示它在神经系统中发挥独特的作用,尤其是神经生长因子(NGF)、脑源性神经营养因子(BDNF)在脑内功能及其表达调控方面具有重要作用。围绝经期妇女随着雌激素水平的降低会产生认知功能的减退,有研究发现去卵巢动物(OVX)雌激素水平降低可以导致某些NGF、BDNF的丢失。通过启动内源性NGF和BDNF的表达而实现对神经元的保护可能为雌激素替代治疗(ERT)脑保护作用的一种机制。本文就近几年的研究进展做一简要综述。     

原发性高血压患者红细胞中存在抗高血压因子

本研究利用热处理和Sephadex G-150凝胶过滤层析等方法,从原发性高血压病患者(EHS)红细胞中部分纯化了抗高血压因子(AHF)。AHF具有热稳定性,分子量大于6kDa;能明显降低卒中易感型自发性高血压大鼠(SHR_(sp))血压,腹腔一次注入AHF(1.6mg/kg)30min后,SHR_(sp)收缩压从原来的27.6±0.7kPa降低到21.4±0.8kPa(p<0.001),4h后收缩压恢复至原水平。AHF能显著抑制自发性高血压大鼠(SHR)和肾性高血压大鼠(RHR)主动脉(A)及肠系膜动脉(MA)血管平滑肌(VSM)Ca~(2 )内流。且对MA Ca~(2 )内流的抑制作用强于A。以上结果表明:EHS红细胞中存在AHF,能显著降低高血压大鼠血压,其降压机制可能与其抑制VSM特别是小动脉VSM Ca~(2 )内流有关。     

Sex Differences in Hypertension: Contribution of the Renin–Angiotensin System

Numerous studies have shown that female human beings exhibit lower blood pressure levels over much of their life span compared with their age-matched counterparts. This sexual dimorphism is apparent in human beings as well as most, if not all, mammals. However, after the onset of menopause blood pressure levels in women increase and become similar to those in men, suggesting an important role of sex hormones in the regulation of blood pressure. The lower blood pressure levels in premenopausal women are associated with a lower risk of development and progression of cardiovascular disease and hypertension compared with age-matched men. This clear female advantage with respect to lower incidence of cardiovascular disease no longer exists after menopause, again highlighting the importance of sex hormones in the pathophysiology of cardiovascular disease in both men and women. In fact, both estrogens and androgens have been implicated in the development of cardiovascular disease and hypertension, with estrogens, in general, being protective and androgens being detrimental. Although the exact mechanisms by which sex hormones contribute to the regulation of cardiovascular function and blood pressure are still being investigated, there is increasing evidence that modulating the activity of locally active hormonal systems is one of the major mechanisms of sex hormone actions in target organs, including the vasculature and kidneys. Indeed, several studies have demonstrated the importance of the interaction between sex hormones and the renin–angiotensin system in regulating cardiovascular function and blood pressure. Furthermore, the differential effects of estrogens and androgens on the expression and activity of the components of the renin–angiotensin system could possibly explain the sex differences in blood pressure levels and the development and progression of cardiovascular disease and hypertension.     

Endogenous cardiotonic steroids and salt-sensitive hypertension

Endogenous cardiotonic steroids (CTS), also called digitalis like factors, have been postulated to play important roles in pathogenesis of hypertension for nearly half of a century. For the past 50 years biomedical scientists have been in quest of an unidentified factor or hormone that both increases blood pressure and renal sodium excretion; this “natriuretic hormone” was, in fact, postulated to interact with the Na/K-ATPase. Recent discoveries have led to the identification of steroid molecules which are present in humans, rodents and amphibians, and which, in a complex manner, interact with each other and with the other systems that regulate renal salt handling and contribute to the salt-sensitivity of blood pressure.Recent findings include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of mechanisms by which CTS can signal through the Na/K-ATPase. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the central regulation of blood pressure and regulation of cell growth, and development of cardiovascular and renal fibrosis in particular.     

Melatonin and the cardiovascular system

Melatonin concentrations in serum, as well as urinary levels of its main metabolite, 6-sulphatoxymelatonin, decrease with age. In the course of aging, the frequency of heart diseases, both acute and chronic, systematically increases. The evidence from the last 10 years suggests that melatonin influences the cardiovascular system. The presence of vascular melatoninergic receptors/binding sites has been demonstrated; these receptors are functionally linked with vasoconstrictor or vasodilatory effects of melatonin. Melatonin can contribute in cardioprotection of the rat heart, following myocardial ischemia. It has been shown that patients with coronary heart disease have a low melatonin production rate, especially those with higher risk of cardiac infarction and/or sudden death. There are clinical data reporting some alterations of melatonin in human stroke and coronary heart disease. The suprachiasmatic nucleus and, possibly, the melatoninergic system may also modulate cardiovascular rhythmicity. Hypercholesterolemia and hypertension are the other age-related symptoms. People with high levels of LDL-cholesterol have low levels of melatonin. It has been shown that melatonin suppresses the formation of cholesterol by 38% and reduces LDL accumulation by 42%. A 10-20% reduction of cholesterol concentration in women using the B-oval pill has been observed. It is a very important because, even a 10-15% reduction in blood cholesterol concentration has bee shown to result in a 20 to 30% decrease in the risk of coronary heart disease. People with hypertension have lower melatonin levels than those with normal blood pressure. The administration of the hormone in question declines blood pressure to normal range. It has been observed that melatonin, even in a dose 1 mg, reduced blood pressure and decreased catecholamine level after 90 min in human subjects. Melatonin may reduce blood pressure via the following mechanisms: 1) by a direct effect on the hypothalamus; 2) as an antioxidant which lowers blood pressure; 3) by decreasing the level of catecholamines, or 4) by relaxing the smooth muscle in the aorta wall.     

假性高血压的研究进展

高血压是心脑血管疾病重要的危险因素,可损伤重要脏器如心、脑、肾的结构和功能,最终导致这些器官的功能衰竭,是危害人类健康的一大杀手。假性高血压(Pseudohypertension,PHT)是指普通袖带测压法所测血压值高于动脉穿刺直接测得的血压值的一种特殊现象,也是难治性高血压的一个主要原因。已有研究表明,假性高血压在老年人、动脉硬化、肾功不全及糖尿病患者中较为多见。目前国内外有限的研究显示假性高血压发病率1.7%-50%。在临床治疗中如不能准确识别假性高血压而对患者行过度降压治疗,将会造成严重的灌注不足事件如中风,甚至死亡。因此,假性高血压日益受到重视,本文就其诊断标准、产生机制、流行病学等方面作一综述。     

Blood pressure modulation and cardiovascular protection by melatonin: potential mechanisms behind

The production of the pineal hormone melatonin is synchronized with day-night cycle via multisynaptic pathway including suprachiasmatic nucleus linking several physiological functions to diurnal cycle. The recent data indicate that impaired melatonin production is involved in several cardiovascular pathologies including hypertension and ischemic heart disease. However, the mechanisms of melatonin effect on cardiovascular system are still not completely understood. The activation of melatonin receptors on endothelial and vascular smooth muscle cells and antioxidant properties of melatonin could be responsible for the melatonin effects on vascular tone. However, the data from in vitro studies are controversial making the explanation of the melatonin effect on blood pressure in vivo difficult. In vivo, melatonin also attenuates sympathetic tone by direct activation of melatonin receptors, scavenging free radicals or increasing NO availability in the central nervous system. The central and peripheral antiadrenergic action of chronic melatonin treatment might eliminate the mechanisms counter-regulating decreased blood pressure, providing thus additional cardioprotective mechanism. The extraordinary antioxidant activity and antilipidemic effects of melatonin may enhance the modulation of blood pressure by melatonin and probably play the most important role in the amelioration of target organ damage by chronic melatonin treatment. Further investigation of these mechanisms should provide novel knowledge about pathophysiological mechanisms of cardiovascular diseases, additional explanation for their circadian and seasonal variability and potentially generate new impulses for the development of therapeutic arsenal.     

Gamma-MSH, sodium metabolism, and salt-sensitive hypertension

Alpha-, beta-, and gamma-melanocyte stimulating hormones (MSHs) are melanotropin peptides that are derived from the ACTH/beta-endorphin prohormone proopiomelanocortin (POMC). They have been highly conserved through evolutionary development, although their functions in mammals have remained obscure. The identification in the last decade of a family of five membrane-spanning melanocortin receptors (MC-Rs), for which the melanotropins are the natural ligands, has permitted the characterization of a number of important actions of these peptides, although the physiological function(s) of gamma-MSH have remained elusive. Much evidence indicates that gamma-MSH stimulates sympathetic outflow and raises blood pressure through a central mechanism. However, this review focuses on newer cardiovascular and renal actions of the peptide, acting in most cases through the MC3-R. In rodents, a high-sodium diet (HSD) increases the pituitary abundance of POMC mRNA and of gamma-MSH content and results in a doubling of plasma gamma-MSH concentration. The peptide is natriuretic and acts through renal MC3-Rs, which are also upregulated by the HSD. Thus the system appears designed to participate in the integrated response to dietary sodium excess. Genetic or pharmacologic induction of gamma-MSH deficiency results in marked salt-sensitive hypertension that is corrected by the administration of the peptide, probably through a central site of action. Deletion of the MC3-R also produces salt-sensitive hypertension, which, however, is not corrected by infusion of the hormone. These observations in aggregate suggest the operation of a hormonal system important in blood pressure control and in the regulation of sodium excretion. The relationship of these two actions to each other and the significance of this system in humans are important questions for future research.     

Redox signaling in central neural regulation of cardiovascular function

One of the most prominent concepts to emerge in cardiovascular research over the past decade, especially in areas focused on angiotensin II (AngII), is that reactive oxygen species (ROS) are critical signaling molecules in a wide range of cellular processes. Many of the physiological effects of AngII are mediated by ROS, and alterations in AngII-mediated redox mechanisms are implicated in cardiovascular diseases such as hypertension and atherosclerosis. Although most investigations to date have focused on the vasculature as a key player, the nervous system has recently begun to gain attention in this field. Accumulating evidence suggests that ROS have important effects on central neural mechanisms involved in blood pressure regulation, volume homeostasis, and autonomic function, particularly those that involve AngII signaling. Furthermore, oxidant stress in the central nervous system is implicated in the neuro-dysregulation associated with some forms of hypertension and heart failure. The main objective of this review is to discuss the recent progress and prospects for this new field of central redox signaling in cardiovascular regulation, while also addressing the molecular tools that have spurred it forward.     

Blood pressure control by home monitoring: meta-analysis of randomised trials

Objective To determine the effect of home blood pressure monitoring on blood pressure levels and proportion of people with essential hypertension achieving targets.Design Meta-analysis of 18 randomised controlled trials.Participants 1359 people with essential hypertension allocated to home blood pressure monitoring and 1355 allocated to the “control” group seen in the healthcare system for 2-36 months.Main outcome measures Differences in systolic (13 studies), diastolic (16 studies), or mean (3 studies) blood pressures, and proportion of patients achieving targets (6 studies), between intervention and control groups.Results Systolic blood pressure was lower in people with hypertension who had home blood pressure monitoring than in those who had standard blood pressure monitoring in the healthcare system (standardised mean difference 4.2 (95% confidence interval 1.5 to 6.9) mm Hg), diastolic blood pressure was lower by 2.4 (1.2 to 3.5) mm Hg, and mean blood pressure was lower by 4.4 (2.0 to 6.8) mm Hg. The relative risk of blood pressure above predetermined targets was lower in people with home blood pressure monitoring (risk ratio 0.90, 0.80 to 1.00). When publication bias was allowed for, the differences were attenuated: 2.2 (-0.9 to 5.3) mm Hg for systolic blood pressure and 1.9 (0.6 to 3.2) mm Hg for diastolic blood pressure.Conclusions Blood pressure control in people with hypertension (assessed in the clinic) and the proportion achieving targets are increased when home blood pressure monitoring is used rather than standard blood pressure monitoring in the healthcare system. The reasons for this are not clear. The difference in blood pressure control between the two methods is small but likely to contribute to an important reduction in vascular complications in the hypertensive population.     

Endpiece: Hospital league tables 1830

ObjectiveTo assess the long term effects of advice to restrict dietary sodium in adults with and without hypertension.DesignSystematic review and meta-analysis of randomised controlled trials.OutcomesMortality, cardiovascular events, blood pressure, urinary sodium excretion, quality of life, and use of antihypertensive drugs.ResultsThree trials in normotensive people (n=2326), five trials in those with untreated hypertension (n=387), and three trials in people being treated for hypertension (n=801) were included, with follow up from six months to seven years. The large high quality (and therefore most informative) studies used intensive behavioural interventions. Deaths and cardiovascular events were inconsistently defined and reported. There were 17 deaths, equally distributed between intervention and control groups. Systolic and diastolic blood pressures were reduced (systolic by 1.1 mm Hg, 95% confidence interval 1.8 to 0.4 mm Hg; diastolic by 0.6 mm Hg, 1.5 to −0.3 mm Hg) at 13 to 60 months, as was urinary 24 hour sodium excretion (by 35.5 mmol/24 hours, 47.2 to 23.9). Degree of reduction in sodium intake and change in blood pressure were not related.ConclusionsIntensive interventions, unsuited to primary care or population prevention programmes, provide only small reductions in blood pressure and sodium excretion, and effects on deaths and cardiovascular events are unclear. Advice to reduce sodium intake may help people on antihypertensive drugs to stop their medication while maintaining good blood pressure control.

What is already known on this topic

Restricting sodium intake in people with hypertension reduces blood pressureLong term effects (on blood pressure, mortality, and morbidity) of reduced salt intake in people with and without hypertension are unclear

What this study adds

Few deaths and cardiovascular events have been reported in salt reduction trialsMeta-analysis shows that blood pressure was reduced (systolic by 1.1 mm Hg, diastolic by 0.6 mm Hg) at 13 to 60 months, with a reduction in sodium excretion of almost a quarter (35.5 mmol/24 hours)The interventions used were highly intensive and unsuited to primary care or population prevention programmesLower salt intake may help people on antihypertensive drugs to stop their medication while maintaining good control of blood pressure, but there are doubts about effects of sodium reduction on overall health