血管紧张素原基因突变与原发性高血压病关系的研究进展

本文在介绍了血管紧张素原基因已知的几种突变与原发性高血压的关系的基础上,对受试者的年龄、性别、高血压病家族史和其它相关基因对研究结果的影响进行了综述,同时也讨论了该基因突变引发高血压的原因。最后就该基因突变与其它相关疾病的关系作了简要介绍。     

血管紧张素基因突变与原发性高血压病关系的研究进展

本文在介绍了血管紧张素原基因已知的几种突变与原发性高血压的关系的基础上,对受试者的年龄、性别、高血压病家族史和其它在基因对研究结果的影响进行了综述,同时也讨论了该基因突变引发高血压的原因。最后就该基因突变与其它相关疾病的关系作了简要介绍。     

DNA甲基化与原发性高血压的研究进展

原发性高血压(简称高血压病)是遗传和环境因素相互作用所导致的一种复杂性疾病.近年来的研究发现,高血压病的发生和发展与DNA甲基化密切相关.11β-HSD-2、ECE-1和AT1b等基因发生甲基化和去甲基化会影响代谢酶和受体的表达,从而通过肾素-血管紧张素-醛固酮系统激活以及肾性水钠潴留等途径引起高血压的发生,这可能是高血压发病的一个重要分子机制.基因组低甲基化(如:高同型半胱氨酸所引起的)会诱发AT1b、ECE-1等受体和代谢酶基因发生去甲基化,从而参与高血压病的发生.深入了解DNA甲基化调控在原发性高血压发病过程中的分子机制及药物代谢酶和受体基因甲基化状态的改变对高血压患者降压疗效的影响,将为临床制定合理化的用药方案提供依据.     

肾素- 血管紧张素- 醛固酮系统与原发性高血压病的关系

目的:探讨血浆肾素-血管紧张素系统与原发性高血压病的关系。方法:采用病例-对照研究设计,入选125例原发性高血压病患者与60例血压正常健康体检者为对照组。采用放射免疫方法测定立位、卧位血浆肾素活性(PRA),醛固酮(ALD)浓度及血管紧张素Ⅱ(AngⅡ)浓度。结果:原发性高血压患者,立位、卧位血浆PRA均低于正常对照组(P<0.05),而ALD浓度及AngⅡ浓度均高于正常对照组(P<0.05)。根据高血压病1级、2级、3级分组,立位、卧位血浆PRA均依次降低(P<0.05);而ALD浓度及AngⅡ浓度依次升高(P<0.05)。结论:肾素-血管紧张素-醛固酮系统与原发性高血压病的发病关系密切,血浆PRA水平、AngⅡ及ALD浓度有望成为原发性高血压病分级的有效指标;降低原发性高血压患者AngⅡ及ALD量是治疗高血压病的关键,血浆AngII、ALD也有望成为评价原发性高血压病疗效的指标。     

miRNA在原发性高血压左心室肥厚中的作用与应用

原发性高血压已经逐渐成为了我国现阶段最受关注的重要公共卫生问题之一,最常见的靶器官损害之一左心室肥厚（left ventricular hypertrophy,LVH）被认为是高血压诱发的心室重塑和高血压心脏病的关键转折点。近年来研究报道,miRNA在原发性高血压的发生与靶器官损害的发展中具有重要的调控作用。本文就miRNA在原发性高血压左心室肥厚发生、诊断、治疗中的研究进展展开综述,旨在为miRNA在原发性高血压左心室肥厚中的调控作用和应用开发理清思路。     

母系遗传性高血压病研究获进展

高血压病是严重危害人类健康的常见疾病,全世界的患病人数已接近10亿,每年有接近760万的患者死于该病。我国每年用于治疗高血压的医疗费高达360多亿元。因此．高血压病是全球亟待解决的重大公共卫生问题和社会问题。母系遗传性高血压病是在临床工作中观察到的高血压病的一种遗传模式,线粒体DNA（mtDNA）突变在其发病过程中可能起到重要的作用,但具体发病机制尚未完全明确。     

脉冲多普勒对高血压病左室舒张功能的监测

本文选自我院92年11月～94年1月期间的高血压门诊中原发性高血压患者126例和正常人群中无心脏器质性病变20例,作为两组比较。运用心脏超声及超声脉冲多普勒检测两组人群的心脏二尖瓣血流速及流速时间积分。用以观察高血压病左室舒张功能的受损状况及评价高血压严重程度对左室舒张功能的影响。结果表明,脉冲多普勒可作为一种监测高血压病左室舒张功能有效手段。且左室舒张功能受损状况与高血压病严重程度呈密切的相关关系。     

哈萨克族原发性高血压患者血浆EPCs CD34^＋水平及其相关性研究

目的：探讨血浆内皮祖细胞（EPCs） CD34＋水平与新疆哈萨克族（哈族）原发性高血压病患者血压、血脂、血糖、肥胖等的相关性。方法：选取新疆哈族原发性高血压患者87为观察组,哈族健康对照组79例,测量血压（BP）、身高、体重、腰围（WC）、臀围（HC）,抽取空腹静脉血测定血糖（FPG）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）,计算体重指数（BMI）腰臀比（WHR）。结果：①原发性高血压组血浆EPCs CD34^＋水平明显低于对照组（p〈0.01）②原发性高血压组血浆EPCs CD34^＋水平与收缩压、舒张压、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、血糖、体重指数呈显著负相关。对照组血浆EPCsCD34^＋水平与收缩压、舒张压、总胆固醇、甘油三酯、体重指数呈负相关。③多元回归分析显示在原发性高血压组中收缩压、甘油三酯是影响血浆EPCs CD34^＋水平的独立因素,在对照组中总胆固醇、体重指数是影响血浆EPCs CD34^＋水平水平的独立因素。结论：哈族原发性高血压患者血浆EPCs CD34^＋水平与血压水平存在一定的相关性。     

高血压病人出院的健康指导

随着社会的发展,各行各业的竞争日益激烈,高血压等心血管病在我国已成为威胁人类健康的“第一杀手”。高血压病又称原发性高血压,是以动脉血压升高,尤其是舒张压持续升高为特点的全身性、慢性血管疾病,容易反复发作。对患者实施心理的护理及出院的健康指导,是预防复发的一项很重要的护理工作。现将健康指导措施总结如下。     

慢性动脉血压调节与原发性高血压病——Ⅰ.慢性动脉血压调节

机体在不同条件下维持动脉血压恒定的机理是不相同的。目前认为,长时程或慢性血压调节的关键器官是肾脏,这种调节与机体的水盐平衡有密切的关系。动脉血压的升高可以导致肾脏排尿量（或排钠量）的升高,即动脉血压与肾脏的排尿量（或排钠量）呈明显的正相关关系,称之为“压力-利尿作用”。当血容量升高时,通过肾脏的压力-利尿作用,可以排出过多的容量,维持动脉血压的恒定。只有在肾脏功能受到损伤的条件下,高血容量才可能引起高血压。     

The role of sodium restriction in the management of hypertension

More than 50 studies have investigated the effect of altered sodium intake on blood pressure. A regression line drawn through the change in blood pressure and change in sodium intake indicates that blood pressure alters about 10 mmHg (1 mmHg = 133.322 Pa) for every 100 mmol/day alteration in sodium intake, a change similar to that observed in between-population "studies." The studies that have failed to show a change in blood pressure have usually been in people with a blood pressure less than 130/90 mmHg. Normotensive people appear to tolerate a higher intake of sodium before blood pressure rises, but if increased sufficiently, blood pressure rises in most people. Sodium restriction reduces blood pressure in people with severe hypertension, moderate hypertension and mild hypertension. It may be the cause of blood pressure increase associated with age and the reason for the higher prevalence of hypertension and vascular disease in Western communities. Sodium restriction should be used to treat people with elevated blood pressure.     

Diseases causing end-stage renal failure in New South Wales.

The nature of the original renal disease was determined in 403 consecutive cases of end-stage renal failure, in 317 of which the clinical diagnosis was corroborated by histological examination of the kidney. Five diseases accounted for 20 or more cases--glomerulonephritis (31% of the total), analgesic nephropathy (29%), primary vesicoureteral reflux (8%), essential hypertension (6%), and polycystic kidneys (5%). In only four cases did renal failure result from chronic pyelonephritis without a demonstrable primary cause. Greater use of micturating cystography and cystoscopy and routine urine testing for salicylate are advocated for earlier diagnosis of the major causes of "pyelonephritis". The incidence of end-stage renal failure in people aged 15-55 in New South Wales was estimated to be at least 34 new cases per million of total population each year.     

Evidence for a circulating sodium transport inhibitor in essential hypertension.

The active sodium transport of white cells and red cells obtained from patients with essential hypertension was impaired. Incubating white cells from normotensive subjects in serum obtained from patients with essential hypertension caused an impairment in sodium transport in the white cells of normotensive subjects similar to that found in the white cells of hypertensive patients. The impairment in sodium transport was due to a fall in the ouabain-sensitive component of the total sodium efflux rate constant. These results show that the serum of patients with essential hypertension contains a substance which influences sodium transport and that it has ouabain-like activity. They also suggest that it is this substance which causes the impairment in sodium transport in the leucocytes of patients with essential hypertension. These findings support the hypothesis that the rise in blood pressure in patients with essential hypertension is due to an increased concentration of a circulating sodium transport inhibitor which is continuously correcting a tendency for sodium retention by the kidney.     

Genetic and familial factors in essential hypertension and related traits

The health significance of essential hypertension “high blood pressure of undefined origin” is well established. It is a major factor contributing to coronary heart disease, stroke, and kidney failure. It directly affects about one in five Americans. Factors which are known to be associated with blood pressure include: body composition as it relates to overall mass and fat mass; physiological variables involving the sympathetic and parasympathetic nervous systems; biochemical variables such as renin, aldosterone, kallikrein, lipids, and lipoproteins, etc.; environmental variables such as sodium intake, heavy metals, and noise; and psychological variables involving personality type and mental stress. There is a definite, well-established genetic involvement in hypertension, but specific genetic mechanisms remain a mystery. Familial aggregation occurs for many of the associated traits listed above. For some, specific polymorphic major genes have been identified, but for others genetic factors are unidentified. Essential hypertension is undoubtedly a heterogeneous group of diseases with the common end result of elevated blood pressure. Because of its health significance, there is considerable interest in identifying genetic mechanisms resulting in essential hypertension. One area that currently shows some potential for the identification of a specific genetic mechanism is related to the transmembrane transport of sodium and potassium cations.     

Intrarenal renin-angiotensin system and counteracting protective mechanisms in angiotensin II-dependent hypertension

It is now well accepted that alterations in kidney function, due either to primary renal disease or to inappropriate hormonal influences on the kidney, are a cardinal characteristic in all forms of hypertension, and lead to a reduced ability of the kidneys to excrete sodium and the consequent development of elevated arterial pressures. However, it is also apparent that many extrarenal factors are important contributors to altered kidney function and hypertension. Central to many hypertensinogenic processes is the inappropriate activation of the renin-angiotensin system (RAS) and its downstream consequences by various pathophysiologic mechanisms. There may also be derangements in arachidonic acid metabolites, endothelium derived factors such as nitric oxide and carbon monoxide, and various paracrine and neural systems that normally interact with or provide a counteracting balance to the actions of the RAS. Thus, when the capacity of the kidneys to maintain sodium balance and extracellular fluid volume within appropriate ranges is compromised, increases in arterial pressure become necessary to re-establish normal balance.     

Renal dopamine receptors and hypertension

Dopamine has been recognized as an important modulator of central as well as peripheral physiologic functions in both humans and animals. Dopamine receptors have been identified in a number of organs and tissues, which include several regions within the central nervous system, sympathetic ganglia and postganglionic nerve terminals, various vascular beds, the heart, the gastrointestinal tract, and the kidney. The peripheral dopamine receptors influence cardiovascular and renal function by decreasing afterload and vascular resistance and promoting sodium excretion. Within the kidney, dopamine receptors are present along the nephron, with highest density on proximal tubule epithelial cells. It has been reported that there is a defective dopamine receptor, especially D(1) receptor function, in the proximal tubule of various animal models of hypertension as well as in humans with essential hypertension. Recent reports have revealed the site of and the molecular mechanisms responsible for the defect in D(1) receptors in hypertension. Moreover, recent studies have also demonstrated that the disruption of various dopamine receptor subtypes and their function produces hypertension in rodents. In this review, we present evidence that dopamine and dopamine receptors play an important role in regulating renal sodium excretion and that defective renal dopamine production and/or dopamine receptor function may contribute to the development of various forms of hypertension.     

Dopaminergic modulation of salt sensitivity in patients with essential hypertension

The present study was designed to investigate the possible role of dopaminergic mechanisms in contributing to the pathogenesis of hypertension in salt sensitive patients. Eighteen patients with essential hypertension were studied while under a diet ranging from low salt to high salt, which enabled a classification in "salt-sensitive" (SS) and "nonsalt-sensitive" (NSS) groups based on a tentative criteria of a 10% increase of mean blood pressure with high salt diet. The SS patients showed reduced urinary excretion of sodium as compared with that from NSS patients. Urinary norepinephrine excretion in all patients with salt loading was suppressed, but urinary excretion of epinephrine showed a tendency to increase in SS patients after salt loading. Urinary excretion of dopamine increased in NSS patients with salt loading, but did not change in SS patients. To further evaluate the role of dopaminergic mechanisms in salt-sensitive hypertension, metoclopramide, a dopamine antagonist, was injected intravenously to all patients. With salt loading, plasma aldosterone levels increased after injection of metoclopramide in NSS patients, but did not change in SS patients. These results suggest that salt-sensitive hypertension is modulated by dopaminergic activity, which in turn is attenuated in SS patients. Decreased dopaminergic activity induced sodium retention both by a direct effect on the kidney as well as indirectly via relatively increased aldosterone secretion. Both mechanisms would help to increase intravascular volume and blood pressure in salt-sensitive hypertension.     

An Assessment of the “Radioactive Renogram” Using O-Iodohippurate Sodium (Hippuran) Labelled with Radioactive Iodine

A “radioactive renogram” using o-iodohippurate sodium (Hippuran)-I¹³¹ was performed in 57 patients who had either hypertension or various renal diseases. In longstanding essential hypertension, the initial uptake and secretory phases are often reduced below normal. In five hypertensive patients who were shown to have unilateral renal disease, the renogram showed significantly abnormal tracings on the affected side. In three patients suffering from ureteral obstruction, the excretory phase was significantly prolonged.On the basis of comparative albumin and iodohippurate renograms, the initial uptake can no longer be considered as a vascular phase, as previously believed.The iodohippurate-I¹³¹ renogram is a useful adjunct in the investigation of hypertension and renal disease, providing information about each kidney not so readily obtained by other means. Nevertheless, the test does not supplant any other investigative procedure and should not be depended upon as a screening procedure.     

Sodium and potassium in essential hypertension.

A study was carried out of arterial pressure and body content of electrolytes in 91 patients with essential hypertension and 121 normal controls. Exchangeable sodium was found to be positively correlated with arterial pressure in the patients, the correlation being closest in older patients; values of exchangeable sodium were subnormal in young patients; and plasma, exchangeable, and total body potassium correlated inversely with arterial pressure in the patients, the correlations being closest in young patients. Three hypotheses were proposed to explain the mechanisms relating electrolytes and arterial pressure in essential hypertension--namely, a cell-salt hypothesis, a dietary salt hypothesis, and a kidney-salt hypothesis. It was concluded that two mechanisms probably operate in essential hypertension. In the early stages of the disease blood pressure is raised by an abnormal process related more closely to potassium than to sodium. A renal lesion develops later, possibly as a consequence of the hypertension. This lesion is characterised by resetting of pressure natriuresis and is manifest by an abnormal relation between body sodium and arterial pressure and by susceptibility to increased dietary sodium intake.