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。     

西他生坦治疗肺动脉高压

肺动脉高压是一种以肺小动脉痉挛、内膜增生和重构为特征的恶性血管疾病。近年来随着对肺动脉高压发病机制深入研究和选择性肺血管舒张药物的研发,肺动脉高压的治疗已经取得极大进步。西他生坦作为一个新型的高选择性内皮素受体拮抗药也因此备受临床关注。西他生坦通过阻断A型内皮素受体,抑制内皮素-1的缩血管效应,舒张血管。本文综述了西他生坦的药理学特点、相关基础及临床研究进展。     

非肽类内皮素受体拮抗剂的研究进展

内皮素具有很强的缩血管作用，与受体结合后可产生广泛的生物学效应，参与了体内多种疾病如高血压、充血性心力衰竭、肾衰、肺动脉高压、转移性前列腺癌和蛛网膜下腔出血等的发生与发展，研究其受体拮抗剂对上述疾病的治疗具有重要意义。本文综述了非肽类内皮素受体拮抗剂的研究进展，并介绍其构效关系。     

内皮素受体拮抗剂在肺动脉高压治疗中的应用

内皮素是强的缩血管因子,肺动脉高压患者内皮素表达明显增加,内皮素受体拮抗剂已经作为靶向药物治疗肺动脉高压,其疗效及前景备受瞩目。波生坦、安立生坦分别为口服的双重和选择性内皮素受体拮抗剂(ERAs),均能显著降低肺动脉高压,改善患者的生存,Macitentan是一种新型的口服非肽类双重ERAs,现已完成Ⅲ期临床研究,疗效可观;西他生坦是选择性的内皮素受体拮抗剂,因其肝脏毒性已经退市。对于这些双重或选择性内皮素受体拮抗剂的选择问题至今仍存在分歧,长期疗效、联合用药及肝脏安全性等问题都需要更多循证医学证实。     

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。     

马西替坦Ⅲ期临床试验资料表明治疗肺动脉高压有效

Actelion公司宣布,其Ⅲ期临床SERAPHIN试验资料表明,内皮素受体拮抗剂马西替坦（macitentan,Op—sumit）治疗肺动脉高压症有效。该试验在全球共入选742名肺动脉高压症患者,随机分到马西替坦3mg组（n=250）、马西替坦10mg组（n=242）和安慰剂组（n=250）。     

治疗肺动脉高压新药Ambrisentan

Ambrisentan是Myogen公司开发的一种用于治疗肺动脉高压（PAH）的高选择性内皮素ETA受体拮抗剂，可强效抑制内皮素所致血管收缩。试验证实。本品生物利用度高，半衰期长，可实现1日1次给药；它明显优于非选择性内皮素受体拮抗剂，药效强，副作用少。其化学结构：     

内皮素受体阻滞剂在糖尿病并发症中的应用*

内皮素是目前已知的缩血管活性最强的生物活性肽之一,通过与内皮素受体结合发挥广泛的生物学活性。内皮素的异常表达与肺动脉高压、前列腺癌、慢性心力衰竭等多种疾病的发生和发展有密切关系。近年来又有大量研究证实内皮素与糖尿病并发症的发生、发展有着重要的关系,内皮素受体阻滞剂可能成为糖尿病并发症治疗的新型药物。现综述内皮素受体阻滞剂在糖尿病并发症中的应用。     

新型内皮素受体拮抗剂马西替坦:治疗肺动脉高压的一线药物

马西替坦是一种新型内皮素受体拮抗剂(ERA),其对内皮素A(ETA)受体和内皮素B(ETB)受体具有双重抑制作用,为肺动脉高压(PAH)的一线治疗药物。在一系列临床研究中均显示出良好的治疗前景,同时安全性及耐受性较好。本文就马西替坦的最新研究进展作一综述。     

先天性心脏病心室间隔缺损患儿血浆内皮素—1水平的变化及其意义

目的 探讨影响先天性心脏病室间隔缺损患儿血浆内皮素－1水平的因素及其临床意义。方法 选择80例先天性心脏病室间隔缺损患儿，其中伴肺动脉高压者52例，轻度肺动脉高压18例，中度肺动脉高压24例，重度肺动脉高压10例。分别采取静脉血，用放射免疫法测定样品中内皮素－1的含量。结果 室间隔缺损患儿血浆内皮素－1水平显著高于对照组（P＜0．01），且伴肺动脉高压者血浆内皮素水平较无肺动脉高压者明显增高（P＜0．01），血浆内皮素含量随肺动脉压力的升高而增加。结论 内皮素－1是先天性心脏室间隔缺损患儿肺动脉高压形成和发展的致病因素之一。     

内皮素受体拮抗剂波生坦与其他药物的相互作用

内皮素受体拮抗剂波生坦是治疗肺动脉高压的有效药物之一。综述波生坦的药动学、药效学特点,以及与其他药物相互作用的机制和临床应用注意事项,并展望了波生坦等内皮素受体拮抗剂的临床应用前景。     

Bosentan: a dual endothelin receptor antagonist

The peptide endothelin plays a significant role in a wide array of pathological conditions, including primary pulmonary hypertension and pulmonary arterial hypertension associated with collagen vascular disease. These are life-threatening conditions that can severely compromise the function of the lungs and heart. Inhibiting the actions of endothelin by blockade of its receptors provides a new and effective approach to therapy for patients with these conditions. Bosentan (Tracleer ) is the first orally-active dual endothelin receptor antagonist and has recently been approved in the US, Canada, Switzerland and the EU for the treatment of pulmonary arterial hypertension. Bosentan significantly improves exercise capacity, symptoms and functional status in patients with this disease and also slows clinical deterioration, which may be indicative of a delay of disease progression. Results from large-scale studies of bosentan in patients with pulmonary arterial hypertension and chronic heart failure have established its long-term safety and tolerability profiles. The introduction of the dual endothelin receptor antagonist bosentan has provided an essential treatment for pulmonary arterial hypertension and ongoing trials are evaluating its potential role in the management of other endothelin-mediated disease states.     

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。     

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.     

Novel therapeutics for the treatment of paediatric pulmonary arterial hypertension

The treatment of paediatric pulmonary arterial hypertension is challenging due to the serious nature of the disease, its rapid progression and the limited treatment options available. However, recent advances in the treatment of pulmonary arterial hypertension may offer significant improvements for patients suffering from this condition. Novel treatment options include prostacyclin analogues and endothelin receptor antagonists. A comprehensive review of the newer agents, with an emphasis on the pathobiology/pathophysiology of pulmonary arterial hypertension provides insight into future management of paediatric pulmonary arterial hypertension.     

Novel therapeutics for the treatment of paediatric pulmonary arterial hypertension

The treatment of paediatric pulmonary arterial hypertension is challenging due to the serious nature of the disease, its rapid progression and the limited treatment options available. However, recent advances in the treatment of pulmonary arterial hypertension may offer significant improvements for patients suffering from this condition. Novel treatment options include prostacyclin analogues and endothelin receptor antagonists. A comprehensive review of the newer agents, with an emphasis on the pathobiology/pathophysiology of pulmonary arterial hypertension provides insight into future management of paediatric pulmonary arterial hypertension.     

Sildenafil for pulmonary arterial hypertension: when blue turns into white

Pulmonary arterial hypertension is a life-threatening, rare disease characterised by vasoconstriction and vascular remodelling of pulmonary artery vessels. Pulmonary arterial hypertension can occur without an obvious cause or can be secondary. Until several years ago, therapeutic approaches were represented mainly by 'conventional therapy' (anticoagulants, calcium channel blockers, diuretics and digoxin, and oxygen therapy). But recently 'specific therapies' (i.e., therapies targeting specific pathogenic pathways) have become available; these are therapies represented by prostacyclin and its derivatives, endothelin receptor antagonists or phosphodiesterase-5 inhibitors. Sildenafil citrate is a phosphodiesterase-5 inhibitor and is the second oral pharmacological agent recently approved for the treatment of pulmonary arterial hypertension. Sildenafil has demonstrated short- and long-term clinical efficacy in the treatment of various forms of pulmonary arterial hypertension, either alone or in combination with other agents, but its safety profile needs further assessment.     

新型肺动脉高压治疗药安贝生坦

安贝生坦是一种口服治疗肺动脉高压的药物,通过选择性抑制内皮素受体A而发挥抑制肺动脉高压的作用。本文对安贝生坦的作用机制、生物活性、药代动力学、安全性及临床试验进展进行综述。     

Sildenafil for pulmonary arterial hypertension: when blue turns into white

Pulmonary arterial hypertension is a life-threatening, rare disease characterised by vasoconstriction and vascular remodelling of pulmonary artery vessels. Pulmonary arterial hypertension can occur without an obvious cause or can be secondary. Until several years ago, therapeutic approaches were represented mainly by ‘conventional therapy’ (anticoagulants, calcium channel blockers, diuretics and digoxin, and oxygen therapy). But recently ‘specific therapies’ (i.e., therapies targeting specific pathogenic pathways) have become available; these are therapies represented by prostacyclin and its derivatives, endothelin receptor antagonists or phosphodiesterase-5 inhibitors. Sildenafil citrate is a phosphodiesterase-5 inhibitor and is the second oral pharmacological agent recently approved for the treament of pulmonary arterial hypertension. Sildenafil has demonstrated short- and long-term clincal efficacy in the treatment of various forms of pulmonary arterial hypertension, either alone or in combination with other agents, but its safety profile needs further assessment.