Jagadeesh G
Division of Cardio-Renal Drug Products, Food and Drug Administration, Rockville, MD 20857, USA.
Indian J Exp Biol. 1998 Dec;36(12):1171-94.
The renin-angiotensin-aldosterone system (RAAS) plays an important role in both the short-term and long-term regulation of arterial blood pressure, and fluid and electrolyte balance. The RAAS is a dual hormone system, serving as both a circulating and a local tissue hormone system (i.e., local mediator) as well as neurotransmitter or neuromediator functions in CNS. Control of blood pressure by the RAAS is exerted through multiple actions of angiotensin II, a small peptide which is a potent vasoconstrictor hormone implicated in the genesis and maintenance of hypertension. Hypertension is a primary risk factor associated with cardiovascular, cerebral and renal vascular disease. One of the approaches to the treatment of hypertension, which may be considered as a major scientific advancement, involves the use of drugs affecting the RAAS. Pharmacological interruption of the RAAS was initially employed in the late 1970s with the advent of the angiotensin converting enzyme (ACE) inhibitor, captopril. ACE inhibitors have since gained widespread use in the treatment of mild to moderate hypertension, congestive heart failure, myocardial infarction, and diabetic nephropathy. As the roles of the RAAS in the pathophysiology of several diseases was explored, so did the realization of the importance of inhibiting the actions of angiotensin II. Although ACE inhibitors are well tolerated, they are also involved in the activation of bradykinin, enkephalins, and other biologically active peptides. These actions result in adverse effects such as cough, increased bronchial reactivity, and angioedema. Thus, the goal of achieving a more specific blockade of the effects of angiotensin II than is possible with ACE inhibition. The introduction of the nonpeptide angiotensin II receptor antagonist losartan in 1995 marked the achievement of this objective and has opened new vistas in understanding and controlling the additional biological effects of angiotensin II. Complementary investigations into the cloning and sequencing of angiotensin II receptors have demonstrated the existence of a family of angiotensin II receptor subtypes. Two major types of angiotensin II receptors have been identified in humans. The type 1 receptor (AT1) mediates most known effects of angiotensin II. The type 2 receptor (AT2), for which no precise function was known in the past, has gained importance recently and new mechanisms of intracellular signalling have been proposed. This review presents recent advances in angiotensin II receptor pharmacology, molecular biology, and signal transduction, with particular reference to the AT1 receptor. Excellent reviews have appeared recently on this subject.
肾素-血管紧张素-醛固酮系统（RAAS）在动脉血压的短期和长期调节以及体液和电解质平衡中发挥着重要作用。RAAS是一个双重激素系统，既是循环激素系统和局部组织激素系统（即局部介质），又在中枢神经系统中发挥神经递质或神经介质的功能。RAAS对血压的控制是通过血管紧张素II的多种作用来实现的，血管紧张素II是一种小肽，是一种强效血管收缩激素，与高血压的发生和维持有关。高血压是与心血管、脑和肾血管疾病相关的主要危险因素。治疗高血压的方法之一，这可被视为一项重大科学进展，涉及使用影响RAAS的药物。20世纪70年代末随着血管紧张素转换酶（ACE）抑制剂卡托普利的出现，RAAS的药理学阻断首次被采用。自那以后，ACE抑制剂在治疗轻度至中度高血压、充血性心力衰竭、心肌梗死和糖尿病肾病方面得到了广泛应用。随着对RAAS在几种疾病病理生理学中作用的探索，人们也认识到抑制血管紧张素II作用的重要性。尽管ACE抑制剂耐受性良好，但它们也参与缓激肽、脑啡肽和其他生物活性肽的激活。这些作用会导致咳嗽、支气管反应性增加和血管性水肿等不良反应。因此，目标是实现比ACE抑制更特异性地阻断血管紧张素II的作用。1995年非肽类血管紧张素II受体拮抗剂氯沙坦的引入标志着这一目标的实现，并为理解和控制血管紧张素II的其他生物学效应开辟了新视野。对血管紧张素II受体的克隆和测序的补充研究表明存在血管紧张素II受体亚型家族。在人类中已鉴定出两种主要类型的血管紧张素II受体。1型受体（AT1）介导血管紧张素II的大多数已知作用。2型受体（AT2）过去其确切功能尚不清楚，最近变得重要起来，并提出了新的细胞内信号传导机制。本综述介绍了血管紧张素II受体药理学、分子生物学和信号转导方面的最新进展，特别提及了AT1受体。最近关于这个主题已经出现了优秀的综述。
