内皮素受体拮抗剂在心血管疾病中的临床应用

本文主要综述了内皮素－１（ＥＴ－１）的生理功能及其在心血管疾病中的病理生理作用，以及内皮素受体的类型和拮抗剂的种类，着重介绍了内皮素受体拮抗剂在心血管疾病中的临床应用。     

内皮素受体拮抗剂治疗肺动脉高压的临床应用进展

内皮素（ET）-1是强有力的内源性血管收缩剂，在肺动脉高压的发病机制中发挥重要作用。ET受体分为两种类型：ETA和ETB。本文综述近年来非选择性ET受体拮抗剂和选择性ETA受体拮抗剂治疗肺动脉高压的临床应用进展。证明ET受体拮抗剂可以改善肺动脉高压患者的运动耐量，降低肺血管阻力，增加心输出量，改善心功能。其主要副作用是血清转氨酶增高。     

内皮素受体拮抗剂在肺动脉高压治疗中的作用

肺动脉高压(PAH)是常见的临床疾病,内皮素(ET)在PAH的发生机制中发挥了重要的作用,临床研究显示,ET受体拮抗剂治疗PAH疗效良好,该类药物可能成为治疗PAH的有效药物.     

内皮素受体拮抗剂用于肺动脉高压的治疗进展

肺动脉高压（PAH）是一类以肺血管阻力进行性升高为主要特征的心肺血管疾病,最终可导致右心衰竭甚至死亡。早期发现PAH患者中内皮素明显高于正常,可引起肺血管的持续收缩及重构。内皮素受体拮抗剂可阻断该通路进而起到降低肺高压的作用。但目前国内临床上对于该类药物了解甚少。本文参考国内外文献对内皮素受体拮抗剂在PAH中的作用机制及临床应用作简要综述,旨在指导临床用药,使更多患者获益。     

内皮素受体拮抗剂治疗心力衰竭的研究进展

内皮素－1是一种由21个氨基酸组成的多肽，是目前已知的最强的缩血管和加压物质。心肌细胞和血管平滑肌细胞产生的内皮素－1可以增加 心肌和血管平滑肌的收缩力，而内皮素系统通过内皮素的过度分泌及其受体的表达上调引起心肌重塑从而导致心力衰竭。有研究表明，对心力衰竭动物进行长期内皮素受体拮抗剂治疗可显著提高存活率。本文综述了内皮素受体拮抗剂治疗心力衰竭的研究进展及其分类和应用前景。     

内皮素受体拮抗剂治疗肺动脉高压症临床评价

目的：伴随对肺动脉高压症发病机制的解释，一类内皮素受体桔抗剂于近期问市，本文阐述其在治疗肺动脉高压症的进展与临床评价，方法：采用国内、外文献综述方法。结果及结论：内皮素受体拮抗剂近年来进展迅猛，其抑制ET-1的收缩血管和促进细胞增殖作用，使动脉高压和心力衰竭问题已不再难于逾越，成为解脱肺动脉高压症之门一把金“药匙”．     

内皮素受体拮抗剂治疗肺动脉高压的研究进展

近年来肺动脉高压的药物治疗多从调控内源性血管收缩因子（如内皮素-1、血栓素A2）和增殖介质（前列腺素和一氧化氮）的失衡入手。本文综述了基于内皮素-1途径的内皮素受体拮抗剂,如波生坦、安立生坦以及新近上市的macitentan,该类药物具有全身副作用小和口服优势,日益受到关注。     

治疗心血管系统疾病的内皮素抑制剂研究进展

心血管疾病是威胁人类健康的头号杀手,发病机制有多种。其中内皮素是迄今为止发现的最强的缩血管多肽,其缩血管作用是AngⅡ的10倍,是肾上腺素的100倍,此外还有细胞增殖和组织纤维化等作用,对高血压、肺动脉高压、动脉粥样硬化、心律失常等心血管疾病的发病机制有着重要影响。从发现内皮素到现在二十多年来,药学工作者对内皮素受体拮抗剂进行了一系列的研究,一些内皮素受体拮抗剂已经上市用于肺动脉高压等心血管疾病的治疗。     

内皮素受体拮抗剂治疗糖尿病肾病研究进展

糖尿病肾病(diabetic nephropathy,DN)是糖尿病(diabetes mellitus,DM)慢性微血管并发症之一,也是导致终末期肾病(end-stage renal disease,ESRD)的主要原因。我国DM相关慢性肾脏病(chronic kidney disease,CKD)患病率已超过肾小球肾炎(glomerulonephritis,GN)相关CKD,DN已成为危害我国居民健康的一大社会问题。DN治疗方案主要为生活方式改变和药物治疗,但目前临床常用药物仅能减轻症状,延缓疾病进展,需新型药物以改善DN患者总体结局。内皮素受体拮抗剂(endothelin receptor antagonist,ERA)是一类近年被应用于DN治疗的新型药物,效果良好。现对ERA在DN治疗中的临床研究进展作一综述,旨在为临床提供参考。     

新型内皮素受体拮抗剂马西替坦

内皮素受体拮抗剂与内皮素受体结合后,可以抑制由内皮素引起的血管收缩,同时还可减轻由内皮素活化造成的血管平滑肌的增殖和纤维化,从而达到治疗与内皮素相关疾病的目的.马西替坦是由瑞士Actelion公司研发的新型内皮素受体拮抗剂,具有组织靶向性,对ETA受体、ETB受体具有双重抑制作用,可用于治疗肺动脉高压、肺纤维化等疾病,在一系列临床研究中显示出良好的治疗前景,且安全性及耐受性均较好.     

内皮素受体阻滞剂的合成研究进展

内皮素具有很强的缩血管作用,与受体结合可产生广泛的生物学效应,它参与了多种心脑血管疾病的发生和发展过程,研究其受体阻滞剂具有重要意义.现综述了不同结构内皮素受体阻滞剂合成研究的进展,供该类新药的合成研发参考.     

Recent discovery and development of endothelin receptor antagonists

Endothelin (ET) receptor antagonists, in particular ET_A selective or ET_A/ET_B balanced antagonists, represent a new therapeutic area for serious diseases such as congestive heart failure (CHF) and pulmonary hypertension. Endothelin antagonists have profound effects on the pulmonary vasculature and the right heart whereas ACE inhibitors primarily affect the peripheral vessel and the left heart. Therefore, combination of endothelin antagonists and ACE inhibitors may be particularly useful in chronic heart failure. Pulmonary hypertension represents another unmet medical need where endothelin antagonists, especially orally-active compounds, show great promise. The importance of this field is evidenced by the number of compounds in clinical trials and by the number of patents filed in recent years. Between January 1997 and April 2000, there are 139 endothelin patents of which 128 are concerned with endothelin receptor antagonists and 11 with endothelin converting enzyme inhibitors. Of the 128 patents, 93 are about new chemical structures, 16 process, 4 formulation, 14 new use or combination therapy and 1 natural product. This article focuses on the 93 novel composition of matter patents in the area of endothelin receptor antagonists.     

Ambrisentan,an endothelin receptor type A-selective endothelin receptor antagonist,for the treatment of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature characterized by vasoconstriction and vascular proliferation, which leads to right heart failure and death. Prostacyclin, NO and endothelin are felt to be key mediators in the development of PAH. We present the available published and presented data about ambrisentan, an ET_A-selective endothelin receptor antagonist (ERA) and newest ERA agent to be approved by the FDA for the treatment of PAH in patients with WHO functional class II and III symptoms. Randomized, placebo-controlled trials have demonstrated a significant improvement in exercise capacity and decrease in time to clinical worsening, along with evidence to support an improvement in WHO functional class and quality of life for patients receiving ambrisentan. Long-term data have shown a 1-year survival of 95%; of the survivors, 94% remained on ambrisentan monotherapy. Endothelin receptor antagonists as a drug class have previously been associated with peripheral edema, aminotransferases abnormalities and a teratogenic risk to a developing fetus. Peripheral edema was observed in patients receiving ambrisentan; however, a greater percentage was experienced in patients aged > 65 years. In contrast, significant aminotransferase abnormalities were not observed with ambrisentan treatment in the placebo-controlled trials, and in all clinical trials combined the 1-year risk seems to be low (< 3%). Despite these data, the FDA requires monthly liver function tests monitoring. As with other ERAs, monthly pregnancy testing is required in all women of child bearing potential.     

双重内皮素受体阻滞剂波生坦

波生坦是一种相对分子质量低的竞争性双重内皮素受体阻滞剂,通过与ETA和ETB的结合来阻止ET-1的作用.它能降低血管压力,阻止心脏和血管增生,减轻肺纤维化和炎症,用于治疗WHO功能组Ⅲ和Ⅳ型肺动脉高压.现综述波生坦的药理学、药动学和临床应用方面的进展.     

Endothelin receptor antagonists in cardiology clinical trials

Endothelin-1 (ET-1) is enhanced and has been demonstrated to be a prognostic marker in patients with advanced stages of heart failure, acute ischaemic syndromes, myocardial infarction and pulmonary hypertension. Activation of the endothelin (ET) system is associated with adverse haemodynamic consequences in patients with congestive heart failure and results in coronary vasoconstriction in patients with coronary artery disease (CAD). Moreover, ET-1 raises blood pressure, induces vascular and myocardial hypertrophy and acts as the natural counterpart of nitric oxide (NO), which exerts vasodilating, antithrombotic and antiproliferative effects. This article reviews recently completed and ongoing clinical trials examining the effects of ET receptor antagonists in patients with heart failure, CAD, arterial hypertension and pulmonary hypertension.     

内皮素受体拮抗剂防治消化性溃疡的研究进展

内皮素(ET)是一种血管张力调节因子,具有极强的血管活性。通过介导ET受体,发挥广泛的生物学活性。然而,ET过度表达将引起胃黏膜组织局部缺血、缺氧、酸中毒等症状,是消化性溃疡形成的重要致病因子之一。因此,ET受体拮抗剂将可能成为治疗消化溃疡的新型药物。现就ET及其受体拮抗剂在消化性溃疡的发生、发展及防治等方面的研究进展进行综述。     

The role of endothelin receptor antagonists in cardiovascular pharmacotherapy

Endothelin (ET) is a hormone produced predominantly by endothelial cells which has been recognised to play a significant role in the development of several cardiovascular disease states. In order to combat the deleterious effects of ET, several ET-receptor antagonists (ETRA) are currently in clinical development. The agents developed thus far inhibit the actions of ET through either selective inhibition of the ET_A receptors or non-selective inhibition of both ET_A and ET_B receptors. However, due to the differing proportions of the two receptor subtypes in various tissues, animal models and pathologies, it remains a matter of debate whether receptor selective agents impart significant clinical benefits over non-selective agents. This paper seeks to briefly summarise the important preclinical and clinical effects that have been reported in the literature and will attempt to provide a rationale for the use of both types of ETRAs in the treatment of both systemic and pulmonary hypertension as well as chronic heart failure (CHF).