血管紧张素转化酶2和其主要产物Ang(1-7)生物作用

肾素-血管紧张素系统（RAS）是一个重要的血压和水电解质调节系统。经典的RAS是指由肝脏分泌的血管紧张素原释放入血液循环，在肾近球细胞产生的肾素作用下转化为10肽的血管紧张素Ⅰ（AngⅠ），再经肺循环的血管紧张素转化酶（ACE）的作用转化为8肽的血管紧张素Ⅱ（AngⅡ）。近年来，研究发现除上述经典（循环RAS）外，局部组织如心脏、血管壁、肾脏、脑等组织还具有独立的RAS，主要凋节局部组织的生长和分化，循环和局部的RAS在心血管疾病中起非常重要的作用。     

ACE2-Ang-(1-7)-Mas轴及其基因学研究进展

肾素-血管紧张素系统(RAS)在心血管、肾脏功能活动调节中起着重要作用,在维持血压稳态、水盐平衡及局部组织器官的正常功能等方面具有重要的作用.……     

肾素-血管紧张素系统与肺部疾病

肾素-血管紧张素系统(renin-angiotensin system,RAS)具有调节血压和水钠平衡的生理作用.近年来,研究发现RAS在多种肺部疾病中发挥作用,例如肺动脉高压、肺纤维化、肺血栓栓塞症和急性呼吸窘迫综合征.最近发现RAS中的血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)是SARS冠状病毒的受体,且病毒感染后ACE2下调可能是SARS患者肺损伤显著加重的原因.这些发现提示RAS与肺部疾病存在重要关系.     

胰腺组织肾素-血管紧张素系统及其作用

<正>肾素-血管紧张素系统(renin angiotensin system,RAS)在调节机体血压、血容量和水电解质平衡方面起着重要的作用。近年研究发现,许多组织器官都存在局部RAS,包括心、肺、肝、肾、脂肪、肾上腺和     

血管紧张素转移酶2-血管紧张素(1-7)-Mas轴在肾脏疾病发病机制中的作用

肾素-血管紧张素系统(RAS)过度兴奋,尤其是肾脏局部RAS高表达对肾脏疾病发生发展起重要作用.随着对RAS深入研究发现,除经典的RAS途径外,还有一条新的RAS途径:血管紧张素转移酶2-血管紧张素(1-7)-Mas轴[ACE2-Ang(1-7)-Mas轴],它和经典RAS相互作用,共同调节机体内环境稳定、维持肾脏功能正常.本文就ACE2-Ang(1-7)-Mas轴在肾脏生理及疾病中的作用及其机制做一简述.     

血管紧张素转换酶-2在肺部疾病中的研究进展

肾素-血管紧张素系统( renin-angiotensin system,RAS)在维持血压和体内水盐平衡方面起重要作用.目前的研究提示RAS与肺纤维化、肺动脉高压等多种呼吸系统疾病的发病机制相关,而血管紧张素转换酶-2(angiot ensin-conver ting enzyme-2,ACE2)是ACE同工酶,起负向调节RAS活性的作用,对急性呼吸窘迫综合征等肺部疾病起保护作用,有望成为呼吸系统疾病治疗的新靶点.     

Ang-(1-7)在急性呼吸窘迫综合征中的肺保护作用

肺组织局部的肾素-血管紧张素系统(RAS)与急性呼吸窘迫综合征(ARDS)关系密切,血管紧张素Ⅱ(AngⅡ)通过其1型受体激活肺部炎症反应,促进ARDS发生发展.血管紧张素-(1-7)[Ang-(1-7)]也是RAS中得重要重要组分之一,能拮抗AngⅡ的生物学作用,被认为是AngⅡ的内源性拮抗剂.在ARDS中,Ang-(1-7)可能通过抑制炎症反应、减轻肺组织纤维化以及抗肺动脉高压等途径发挥肺保护作用,在ARDS中具有广阔的应用前景.     

肾素-血管紧张素系统与胰腺炎

循环肾素一血管紧张素系统（RAS）是复杂的神经内分泌系统，也是应激反应系统，在维持机体血压和水、电解质平衡中发挥重要作用。血管紧张素原由肝脏产生，在肾脏产生的肾素作用下转换为血管紧张素Ⅰ（AngⅠ），由肺脏产生的血管紧张素转换酶（ACE）转换为血管紧张素Ⅱ（AngⅡ），在其他一些酶的作用下还可以产生其他一些活性物质，如AngⅡ、AngⅣ（Ang3～8）和Ang1～7，AngⅡ是主要的活性物质。血管紧张素受体包括AT1、AT2、AT3、AT4四种，AT1又分两个亚型，AT1a和AT1b。已知大部分AngⅡ活性是由AT1受体介导的。最近研究证明，很多组织器官存在局部RAS，如大脑、心脏、肾脏、性腺、肾上腺、胰腺等，这种组织RAS独立地通过旁分泌和（或）自分泌方式在各自组织器官的生理和病理生理过程中发挥重要作用，应用局部组织RAS拮抗剂可对这些组织器官疾病产生积极作用。[第一段]     

肾素-血管紧张素系统与肝纤维化

肾素 -血管紧张素系统 (RAS) ,其最主要的生物活性肽为血管紧张素Ⅱ (AⅡ )。在循环与组织局部中均存在RAS。循环中的RAS主要参与AⅡ的急性反应包括调节血压、心律、血管收缩、肾小球水钠潴留及体液平衡等生理功能。而组织局部的RAS则主要参与AⅡ介导的长期生理作用包括细胞生长、分化、增殖等[1] 。本文拟阐述循环与肝组织局部的RAS在肝纤维化发生、发展过程中的病理生理作用及临床意义。1　肝组织内存在局部的肾素 -血管紧张素系统有研究[2 ] 证实 ,肝脏是循环中血管紧张素原的主要来源 ,AⅡ可刺激肝细胞对其合成分泌。Kon发现[3 …     

肾素血管紧张素系统和血管紧张素Ⅱ信号转导机制的研究进展

肾素血管紧张素系统 (RAS)是一个重要的水电解质平衡调节系统。近年来 ,研究发现除循环RAS外 ,局部组织如心脏、血管壁、肾脏、脑等也具有独立的 RAS,主要调节局部组织的生长和分化 [1]。而且除 Ang 外 ,血管紧张素 1 - 7(Ang1 - 7)也是 RAS中的重要生物活性成分 ,对 Ang 具有反向调节作用 [2 ]。同时 ,随着细胞和分子生物学的发展 ,人们对 Ang 的生成途径和其作用机制有了更加深入的认识 ,对 Ang 信号转导机制的研究取得了一些重大进展。1　RAS以往认为 RAS的主要成分为血管紧张素原、肾素、Ang 、ACE、和 Ang ,近年又增加了 A…     

局部肾素血管紧张素系统与肺癌的研究进展

肺癌的发生发展是多因素造成的,治疗和预防也是多方面的.近年来,随着对肾素血管紧张素系统(RAS)逐步深入的研究,RAS得到了很大的更新,发现了许多新的组分,而且发现除了系统性的RAS外,肺癌局部组织微环境中也包含重要的RAS组分,并在肿瘤的发生发展及血管生成中发挥重要作用.本文就更新后的局部RAS与肺癌的发生发展机制作...     

Interactions between antihyperglycemic drugs and the renin-angiotensin system: Putative roles in COVID-19. A mini-review

BackgroundDiabetes mellitus is associated with a more severe course of coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes angiotensin-converting enzyme II (ACE2) receptor for host cell entry. We aimed to assess the interactions between antihyperglycemic drugs and the renin-angiotensin system (RAS) and their putative roles in COVID-19.MethodsA literature search was performed using Pubmed to review the interrelationships between hyperglycemia, RAS and COVID-19, and the effects of antihyperglycemic medications.ResultsThe RAS has an essential role in glucose homeostasis and may have a role in COVID-19-induced lung injury. Some antihyperglycemic medications modulate RAS and might hypothetically alleviate the deleterious effect of angiotensin II on lung injury. Furthermore, most antihyperglycemic medications showed anti-inflammatory effects in animal models of lung injury.ConclusionsSome antihyperglycemic medications might have protective effects against COVID-19-induced lung injury. Early insulin therapy seems very promising in alleviating lung injury.     

Local renin-angiotensin system in the pancreas: the significance of changes by chronic hypoxia and acute pancreatitis

The circulating renin-angiotensin system (RAS) plays an important role in the maintenance of blood pressure and fluid homeostasis. Recently, there has been a shift of emphasis from the circulating RAS to the local RAS in the regulation of individual tissue functions via a paracrine and/or autocrine mechanism. In fact, a local RAS has been proposed to be present in an array of tissues including the brain, heart, kidney and gonads. Our previous studies have provided solid evidence that several key elements of the RAS, notably angiotensinogen and renin, are present in the rat pancreas. The data support the existence of an intrinsic RAS in the pancreas and this local RAS may be important for the exocrine/endocrine functions of the pancreas. Interestingly, such a pancreatic RAS has been demonstrated to be markedly activated by experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic RAS by chronic hypoxia and experimental pancreatitis could play a role in the physiology and pathophysiology of the pancreas. The significant changes of pancreatic RAS may have clinical relevance to acute pancreatitis and hypoxia-induced injury in the pancreas.     

Intrarenal renin-angiotensin system

Phylogenetically the renin-angiotensin system (RAS) is an ancient regulatory system which has attracted the attention of researchers for about a century. As a result of their efforts, different types of RAS inhibitors are now widely used as therapeutic medicines. The scientific enthusiasm toward RAS remains undiminished and new findings and discoveries are to be expected. Early investigators described the role of RAS in the local control of renal hemodynamics. This correlated well with the morphology of juxtaglomerular apparatus (JGA). Recently developed imaging techniques has allowed for in vivo visualization of cellular functions and the use of molecular biological tools have shed new light on the morphology and physiology of renal RAS, especially in connection with the tubular system. RAS has gained recognition to be more than just an endocrine regulatory system for regulating hemodynamics and water/salt metabolism. RAS is a local tissue and/or cellular regulator with a wide range of effects exerted via various receptors. Local RAS is crucially involved in basic physiological processes like ontogenesis and cell proliferation as well as pathophysiological conditions such as inflammation and tissue fibrosis. These findings may open new frontiers for novel therapeutic approaches. This review focuses only on some specific - less discussed and recently described or hypothesized - morphological and functional aspects of intrarenal RAS, including in vivo imaging of RAS, its effects on juxtaglomerular apparatus and possible cooperative mechanisms among various local renal RAS systems.     

The renin-angiotensin system and the long-term complications of diabetes: pathophysiological and therapeutic considerations.

The relationship between the renin-angiotensin system (RAS) and the progression of diabetic renal disease has been a major focus of investigation over the past 20 years. More recently, experimental and clinical studies have also suggested that the RAS may have a pathogenetic role at other sites of micro- and macrovascular injury in diabetes. Complementing major advances into the understanding of the local, as distinct from the systemic RAS, a number of large clinical trials have examined whether blockade of the RAS might provide protection from the long-term complications of diabetes, beyond that due to blood pressure reduction alone. While some controversy remains, these studies have, in general, suggested that angiotensin converting enzyme (ACE) inhibition and more recently, angiotensin receptor blockade reduce the development and progression of diabetic nephropathy, cardiovascular disease and possibly retinopathy. This review will focus on recent developments in our understanding of the tissue-based RAS and its role in end-organ injury in diabetes, the results of recent clinical trials and newer strategies for the pharmacological manipulation of the RAS.     

Mitigation of radiation induced pulmonary vascular injury by delayed treatment with captopril

Background and Objective: A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin‐converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2 months post‐exposure. In this study, we evaluate the potential of a renin‐angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage. Methods: Rats exposed to 10 Gy thorax only irradiation and age‐matched controls were studied 2 months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2 weeks after radiation exposure, with two doses of the ACE inhibitor, captopril, dissolved in their drinking water. To determine pulmonary vascular responses, we measured pulmonary haemodynamics, lung ACE activity, pulmonary arterial distensibility and peripheral vessel density. Results: Captopril, given at a vasoactive, but not a lower dose, mitigated radiation‐induced pulmonary vascular injury. More importantly, these beneficial effects were observed even if drug therapy was delayed for up to 2 weeks after exposure. Conclusions: Captopril resulted in a reduction in pulmonary vascular injury that supports its use as a radiomitigator after an unexpected radiological event such as a nuclear accident.     

Natural killer cell activity in a rat model of amiodarone-induced interstitial lung disease

The role of lymphocytes in the pathogenesis of amiodarone-induced lung disease is controversial. Increases in the percentages of lymphocytes in bronchoalveolar fluid of both patients and animals with amiodarone pulmonary toxicity have been reported. To assess whether these lymphocytes are functionally activated, we measured natural killer cell activity in the lungs and blood of rats with amiodarone-induced pulmonary toxicity. Amiodarone treated rats exhibited pathologic evidence of amiodarone-induced lung disease after one week of treatment and this injury was sustained and more extensive during the remainder of the study period. Control rats had histologically normal lungs. Blood NK activity was equally present in both amiodarone-treated and control groups and was not significantly different over the course of the study (16 +/- 3 percent and 13 +/- 2 percent, respectively; p greater than 0.05). Thus, NK cells were activated only in the lungs of rats treated with amiodarone, suggesting a local immune response in the lung. These data support the concept that lymphocytes play an important role in the pathogenesis of amiodarone-induced lung disease.     

Adult stem cells for chronic lung diseases

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lung diseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lung diseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow‐derived mesenchymal stem cells (B‐MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B‐MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B‐MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B‐MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF.