血管紧张素转换酶抑制剂在心血管疾病中的应用

肾素-血管紧张素系统（RAS）是由肾脏和肝脏分泌的一组相互作用又互相调节的激素或前体,包括肾素,血管紧张素原（Ang）,血管紧张素Ⅰ（Ang Ⅰ）,血管紧张素Ⅱ（AngⅡ）,血管紧张素转化酶（ACE）,血管紧张素受体（AT-1和AT-2受体）等.RAS不仅是存在于血液循环的激素系统,还具有旁分泌和自分泌的作用,且许多组织中（心、脑、肾等）还存在局部的RAS,在器官、组织和细胞的功能调节中具有重要的作用.ACEI抑制生物活性低的AngⅠ转换成生物活性高的AngⅡ,阻止缓激肽灭活而起到对抗AngⅡ和增加缓激肽的作用,在心血管疾病治疗中起到重要作用.     

肾脏局部RAS与糖尿病肾病关系的研究进展

肾素-血管紧张素系统（RAS）主要是由肾素（RA）、血管紧张素Ⅰ（AngⅠ）、血管紧张素Ⅰ转化酶（ACE）、血管紧张素Ⅱ（AngⅡ）、血管紧张素Ⅱ受体以及血管紧张素（1-7）和血管紧张素转化酶相关羧肽酶（ACE2）等组成的具有多元生物活性的系统。Mulrow的研究提示肾脏局部不同于全身RAS它属于具有独立作用的系统,它通过旁分泌和自分泌形式发生作用,通过调节肾脏血流动力学及其它机制参与肾脏多种疾病的病理生理过程。     

肾素-血管紧张素系统阻断剂在慢性肾脏病中的应用

肾功能逐渐丧失和心血管疾病高发风险是影响慢性肾脏病（CKD）患者预后的两个重要因素,故CKD治疗的主要目的就是要保护肾脏和心血管系统,延缓肾脏病变进展,预防心血管事件发生。肾素-血管紧张素系统阻断剂即血管紧张素转换酶抑制剂（ACEI）和血管紧张素Ⅱ受体阻断剂（ARB）是目前具有肾脏和心血管保护作用证据最多的治疗药物。本文就肾素-血管紧张素系统（RAS）及RAS阻断剂对肾脏的保护作用和在CKD中的应用作一简述。     

肾素-血管紧张素系统与肾小球硬化

各种慢性肾脏损害,不管其基本病因如何,共同结局是肾小球硬化。在对人类肾脏疾病以及动物实验的研究中发现,肾素．血管紧张素系统(renin-angiotensin system,RAS)在肾脏疾病的发生发展中起着特别重要的作用。RAS的过度兴奋,不仅促使血压上升,更由于其对肾小球出现小动脉的选择性的作用,致使肾小球内毛细血管的跨膜压明显升高。另外,血管紧张素Ⅱ     

血管紧张素受体拮抗剂在慢性肾脏病中的应用

目前,已经公认血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)与许多肾脏疾病的发展过程密切相关。随着对肾素-血管紧张素系统(ReninAngiotensinSystem,RAS)的主要效应因子AngⅡ及血管紧张素受体的深入研究,血管紧张素受体拮抗剂(Angiotensin Receptor Blockers,ARB)因能更完全地阻断RAS,因此,在肾脏疾病的治疗中逐步得到应用。本文对近年来ARB药物的特点、在治疗肾脏疾病中的应用等问题做一介绍。     

血管紧张素转化酶2的研究进展

肾素一血管紧张素系统（renin—angiotensin system,RAS）是一复杂的调节系统,在维持机体血压稳定和水电解质平衡中发挥了主导作用,RAS活性的增强与心血管病以及由这些疾病所致的脏器损害（如：心脏、血管、肾脏等）存在相关性。血管紧张素转化酶（ACE）是肾素一血管紧张素系统的重要调节酶,而血管紧张素转化酶2（angiotensinconverting enzyme2,ACE2）是近年新发现的与ACE具有较高同源性的酶,     

血管紧张素转换酶抑制剂与血管紧张素受体拮抗剂的比较

在肾素血管紧张素系统(RAS)中,血管紧张素Ⅱ(AngⅡ)刺激机体引起许多生理的反应,以维持血压及肾脏的功能,在高血压、动脉疾病、心脏肥大、心力衰竭以及糖尿病、肾病等发病机制上都起着重要的作用。血管紧张素转换酶抑制剂(ACEI)可以部分阻断AngⅡ的形成,对上述心血管病产生了显著的治疗效果。ACEI应用于临床已20余年,已有许多大的临床试验证实其能有效降低血压,若联合利尿剂疗效更佳。ACEI治疗心     

血管紧张素Ⅱ受体拮抗剂临床应用进展

血管紧张素Ⅱ受体拮抗剂（ATⅡRa）是一类作用于肾素-血管紧张素系统（RAS）的一类新型抗高血压药，与ACEI相比，能更充分、更直接、更具选择性地阻断RAS，且不良反应更少，目前应用正日趋广泛，已被列为六大类抗高血压药物之一。     

血管紧张素Ⅱ受体拮抗剂

肾素-血管紧张素系统（RAS）在血压的调节及维持体液平衡中起着关键性作用，血管紧张素Ⅱ（AugⅡ）是RAS中维持和升高血压的主要介质——迄今已知的最强的内源性收缩血管因子之一。它作用于特异性的受体，导致血管收缩和醛固酮释放，在长期的血压调节中就是通过RAS的AugⅡ发挥关键作用。至今RAS的各种阻滞剂广泛应用于高血压和充血性心力衰竭的治疗和研究中，第一类是熟知的血管紧张素转换酶抑制剂（ACEI），第二类是即将推向临床的竞争性aug巨受体的桔抗剂，第三类正在研究中的选择性肾素抑制剂。但是，就最直接地阻抗和阻滞RAS作…     

血管紧张素Ⅱ受体拮抗剂研究进展

随着对肾素-血管紧张素系统(RAS)在心血管病发病学中的作用和重要性的进一步了解[1],血管紧张素转换酶抑制剂(ACEI)不断发展并被广泛应用,血管紧张素Ⅱ(Aug Ⅱ)受体拮抗剂也从多方面确立了其重要地位。目前国外正抓紧开发AngⅡ受体拮抗剂,部分已在临床应用并取得较好的疗效[1-3]。本文从 Ang Ⅱ及Ang Ⅱ受体拮抗剂治沙坦(Losartan)及其与ACEI的区别进行讨论。 血管紧张素Ⅱ 1.Ang Ⅱ的作用 RAS在调节血压、维持机体体液和电解质平衡中起作用,许多心血管病的发生与发展与其密切相关。目前的研究证实,除体循环的RAS外,心脏、血管、…     

Pharmacology of the angiotensin II receptor antagonist,eprosartan

The non-peptide angiotensin II receptor antagonists represent a new class of drugs with demonstrated efficacy in the treatment of hypertension. Eprosartan is a potent, orally active AT₁ receptor antagonist which is chemically distinct from losartan and other non-peptide angiotensin II receptor antagonists. Eprosartan has a high affinity for the angiotensin II AT₁ receptor, but does not interact with the AT₂ receptor, adrenergic receptors or other receptors involved in cardiovascular regulation. In contrast to most other angiotensin II antagonists, eprosartan is a true competitive antagonist of the AT₁ receptor. Eprosartan is effective in antagonising the cardiovascular and renal effects of exogenous angiotensin II in both experimental animals and humans. Furthermore, it is an effective antihypertensive agent when administered to renin-dependent hypertension animal models, and in patients with mild to severe hypertension. The antihypertensive effect of eprosartan is maintained over a 24-h interval following a single dose with no reported dose-dependent adverse side-effects.     

血管紧张素受体阻滞剂治疗慢性进展性肾病的研究进展

肾素-血管紧张素系统(RAS)在慢性肾病的进展中起着非常重要的作用。阻断RAS作用已成为慢性进展性肾病(CPRD)治疗的主要手段之一。血管紧张素受体阻滞剂(ARB)以其副反应小、安全性高等特点受到广泛关注。近十年的研究表明ARB可以从多方面确实有效地延缓慢性肾病的进展，并为CPRD的临床治疗提供了循证医学证据。     

End-organ protection in patients with hypertension: focus on the role of angiotensin receptor blockers on renal function

The renin-angiotensin system (RAS) plays a key role in a number of pathophysiological mechanisms that are involved in the development and progression of cardiovascular and renal disease. For these reasons, pharmacological antagonism of this system, particularly the blockade of formation or the receptor antagonism of angiotensin II, has been demonstrated to be an effective and safe strategy to reduce the burden of cardiovascular disease. Among different drug classes, angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) have provided an excellent alternative to ACE inhibitors, representing a more selective and a better tolerated pharmacological approach to interfere with the RAS. Results derived from large, international, randomized clinical trials have consistently indicated that ARB-based therapeutic strategies may effectively provide cardiovascular and renal disease prevention and protection in different clinical conditions across the entire cardiovascular continuum. This article reviews the pathophysiological rationale of RAS involvement in the pathogenesis of renal diseases, focusing on the beneficial effects provided by ARBs in terms of renal protection.     

Similar renoprotection after renin‐angiotensin‐dependent and ‐independent antihypertensive therapy in 5/6‐nephrectomized Ren‐2 transgenic rats: are there blood pressure‐independent effects?

1. Hypertension plays a critical role in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD), but it has also been postulated that antihypertensive drugs that block the renin-angiotensin system (RAS) show class-specific renoprotective actions beyond their blood pressure (BP)-lowering effects. 2. Because this notion has recently been questioned, in the present study we compared the effects of a RAS-dependent antihypertensive therapy (a combination of trandolapril, an angiotensin-converting enzyme inhibitor (ACEI) and losartan, an angiotensin-II (AngII) receptor subtype 1A receptor antagonist) with a 'RAS-independent' antihypertensive therapy (a combination of labetalol, an alfa- and beta-adrenoreceptor antagonist with the diuretics, hydrochlorothiazide and furosemide) on the progression of CKD after 5/6 renal ablation (5/6 NX) in Ren-2 renin transgenic rats (TGR), a model of AngII-dependent hypertension. Normotensive transgene-negative Hannover Sprague-Dawley (HanSD) rats after 5/6 NX served as controls. 3. RAS-dependent and -independent antihypertensive therapies normalized BP and survival rate, and prevented the development of cardiac hypertrophy and glomerulosclerosis to the same degree in 5/6 NX HanSD rats and in 5/6 NX TGR. The present findings show that renoprotection, at least in rats after 5/6 NX, is predominantly BP-dependent. When equal lowering of BP was achieved, leading to normotension, cardio- and renoprotective effects were equivalent irrespective of the type of antihypertensive therapy. 4. These findings should be taken into consideration in attempts to develop new therapeutic approaches and strategies aimed to prevent the progression of CKD and to lower the incidence of ESRD.     

Therapeutic potential of angiotensin II receptor antagonists

The circulating renin-angiotensin system plays an important role in cardiovascular homeostasis. More importantly, the local tissue renin angiotensin plays a pivotal role in cell growth and remodelling of cardiomyocytes and on the peripheral arterial vasculature. In addition, the renin angiotensin system is related to apoptosis, control of baroreflex and autonomic responses, vascular remodelling and regulation of coagulation, inflammation and oxidation. The cardioprotective and vascular protective effects of the angiotensin receptive blockade appears to be related to selective blockade of the angiotensin II (A-II) Type I (AT₁) receptors. However, there is now growing evidence showing that some of the effects of AT-II receptor blockers (ARBs) are related to the activation of the kinin pathways. This paper will review some of the recent mechanisms related to the cardiovascular effects of angiotensin and more specifically of ARBs. This paper will present the novel data on the role of ARB in the development of atherosclerosis, vascular remodelling, coagulation balance and autonomic regulation. Finally, the role of ARBs, used alone or in combination with ACE inhibitor in patients with heart failure, will be discussed.     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: ENDOGENOUS ANGIOTENSIN II LEVELS AND THE MECHANISM OF ACTION OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR TYPE 1 ANTAGONISTS

• 1 Modification of endogenous angiotensin II (AngII)-mediated processes by inhibitors of the angiotensin-converting enzyme (ACE) and antagonists of the angiotensin type 1 (AT₁) receptor is dependent upon both the levels of each agent in the plasma and tissues and on the concomitant changes in plasma and tissue AngII levels.
• 2 Both ACE inhibitors and AT₁ receptor antagonists increase renin secretion and angiotensin peptide formation in plasma and extrarenal tissues. Clinical doses of ACE inhibitors produce incomplete inhibition of ACE and the increased AngI levels act to restore AngII towards basal levels. Clinical doses of AT₁ receptor antagonists produce incomplete blockade of AT₁ receptors and the increased AngII levels in plasma and extrarenal tissues counteract (to an unknown degree) the effects of the antagonist.
• 3 The effects of ACE inhibitors and AT₁ receptor antagonists on AngII levels show tissue specificity. Angiotensin II-mediated processes in the kidney are most sensitive to inhibition by these agents. ACE inhibitors reduce renal AngII levels at doses much less than those required to reduce AngII levels in plasma and other tissues. Moreover, in contrast to increased AngII levels in plasma and extrarenal tissues, renal AngII levels do not increase in response to AT₁ receptor antagonists. The inhibition of AngII-mediated processes in the kidney may, therefore, play a primary role in mediating the effects of ACE inhibitors and AT₁ receptor antagonists on blood pressure and other aspects of cardiovascular function and structure.
• 4 Combination of an ACE inhibitor with an AT₁ receptor antagonist prevents the rise in plasma AngII levels that occurs with AT₁ receptor antagonism alone. This combination would, therefore, be predicted to produce more effective inhibition of endogenous AngII-mediated processes than either agent alone. We must await further studies to determine whether the combination of ACE inhibition and AT₁ receptor antagonism results in superior clinical outcomes.

     

β-抑制蛋白在AT_1受体信号通路中的作用及意义

血管紧张素Ⅱ(AngⅡ)是肾素-血管紧张素系统的重要活性物质,广泛参与心血管活动的调节。AngⅡ通过与其受体结合,诱导激活复杂的胞内信号通路,是其参与多种病理生理过程的基础。β-抑制蛋白(β-arrestins)是一类负反馈调节G蛋白偶联受体的多功能蛋白,广泛存在心血管系统,是近期的研究热点。该文主要综述β-抑制蛋白在AngⅡ诱导的AngⅡ一型受体(AT1受体)信号通路中的作用及意义。     

血管紧张肽Ⅱ受体拮抗药厄贝沙坦在高血压治疗中的应用

厄贝沙坦是一种新型的选择性血管紧张肽Ⅱ受体1拮抗药。通过抑制血管紧张肽Ⅱ与其受体1的结合,厄贝沙坦可对心血管系统发挥多种保护作用。厄贝沙坦具有明确的降压作用,并有抑制左室肥厚的作用。厄贝沙坦另有重要的肾脏保护作用,可延迟糖尿病肾病的发生。     

Novel angiotensin II inhibitors in cardiovascular medicine

Blockade of the renin-angiotensin-aldosterone cascade is now recognised as a very effective approach to treat hypertensive, heart failure and high cardiovascular risk patients and to retard the development of renal failure. The purpose of this review is to discuss the state of development of currently available drugs blocking the renin-angiotensin system, such as angiotensin converting enzyme (ACE) inhibitors, renin inhibitors and angiotensin II receptor antagonists, with a special emphasis on the results of the most recent trials conducted with AT₂ receptor antagonists in heart failure and Type 2 diabetes. In addition, the future perspectives of drugs with dual mechanisms of action, such as NEP/ACE inhibitors, also named vasopeptidase inhibitors, are presented.     

Pharmacokinetic evaluation of losartan

INTRODUCTION: Blockade of the renin-angiotensin system is one of the major therapeutic strategies in the management of patients with essential hypertension, congestive heart failure and diabetic as well as non-diabetic renal diseases. As the first angiotensin II receptor blocker (ARB) on the market, losartan belongs to the most frequently prescribed ARB. AREA COVERED : The present review examines the pharmacokinetics of losartan with a special discussion on the dose of losartan that should be used in clinical practice to obtain the maximal benefits of the drug. Readers are provided with arguments suggesting that the dose of 50 mg losartan is probably too low and that losartan should preferably be prescribed at the dose of 100 mg/day or higher. EXPERT OPINION : Losartan is an effective antagonist of angiotensin II AT(1) receptors which has been shown to provide important clinical benefits in patients with hypertension, congestive heart failure and renal diseases. Losartan should be prescribed at the dose of 100 mg/day and the use of higher doses should be reconsidered in future studies to improve its clinical efficacy.