作用于RAAS的抗高血压药研究进展

综述作用于肾素 -血管紧张素 -醛固酮系统 (RAAS)的抗高血压药研究进展 ,分别介绍血管紧张素转化酶抑制剂、血管紧张素Ⅱ受体拮抗剂及肾素和醛固酮抑制剂的药理作用、不良反应以及若干目前临床常用或正在研发中的相应药物及其特点。作用于RAAS药物的研发为治疗高血压提供了更多的选择。     

肾素-血管紧张素系统抑制在高血压药物治疗中的意义

近年多项临床研究提示了积极有效控制血压对高血压患者的重要性。肾素-血管紧张素系统(RAS)是高血压治疗的重要靶点,具血管紧张素受体阻断或血管紧张素转化的抑制作用的 RAS 抑制剂,对高血压患者临床转归终点事件的预后具有重要意义。     

肾素-血管紧张素-醛固酮系统抑制剂的作用机制

肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system,RAAS)是一种调控心血管和肾功能的复杂的网络系统。RAAS的激活在高血压、急性心肌梗死后的心肌重塑、急性和慢性心力衰竭以及肾功能不全等多种疾病的进展中起着重要的作用,而RAAS抑制剂能够显著延缓上述疾病的进展和改善患者的预后。本文就目前临床常用的几类RAAS抑制剂的作用机制作一概述。     

肾素-血管紧张素系统抑制剂治疗高血压的研究进展

高血压是引起心血管疾病和导致死亡的最主要原因之一。肾素-血管紧张素系统在高血压的病理生理机制中起着关键作用。肾素-血管紧张素系统抑制剂在治疗高血压中的应用最为广泛。已有许多大型临床研究评价了血管紧张素转化酶抑制剂、血管紧张素Ⅱ受体拮抗剂和肾素抑制剂单用或联用治疗高血压的作用。本文就近年来肾素-血管紧张素系统抑制剂治疗高血压的研究进展作一综述。     

螺内酯对难治性高血压患者RAAS指标的影响研究

目的 探究螺内酯对难治性高血压患者肾素-血管紧张素-醛固酮系统(RAAS)指标的影响.方法 选择2013年1月-2014年12月仙桃市第-人民医院收治的116例难治性高血压作为研究对象,随机分为观察组和对照组各58例.对照组接受常规治疗,观察组在常规治疗基础上服用螺内酯.治疗后,分析两组RAAS指标(肾素活性、血管紧张素Ⅱ以及醛固酮水平)变化情况及临床效果.结果 两组治疗10周后较治疗前肾素活性、血管紧张素Ⅱ以及醛固酮水平比较均显著降低(P＜0.05);观察组较对照组水平均显著降低(P＜0.05);治疗5周及10周后观察组显效率及总有效率均高于对照组(P＜0.05).结论 螺内酯可以有效地将交感神经活性阻断,降低RAAS指标,其机制可能是通过阻断肾素、血管紧张素Ⅱ以及醛固酮三者的产生,起到协同降压的效果.     

血管紧张素Ⅱ受体拮抗药的临床应用与不良反应

随着人们对肾素-血管紧张素-醛固酮系统（RAAS）认识的不断深入，血管紧张素Ⅱ受体拮抗药（ARB）已成为一类重要的高血压治疗药物，是继血管紧张素转换酶抑制剂（ACEI）后，又一类作用于肾素-血管紧张素系统（RAS）的新型降压药，具有高效、长效、安全、可口服、耐受性好等特点。ARB属非肽类化合物，目前经美国食品与药品管理局（H）A）批准应用于临床的ARB有氯沙坦、缬沙坦、伊贝沙坦、替米沙坦、坎地沙坦、     

新颖抗高血压药物——口服肾素抑制剂阿利克仑

肾素-血管紧张素-醛固酮系统（RAAS）作为心功能的主要调节者，其重要作用已自拮抗这一系统的药物如血管紧张素转化酶（ACE）抑制剂、血管紧张素受体阻滞剂（ARB）和醛固酮拮抗剂在目前心血管疾病管理中的地位而得到相当佐证。大量临床研究业经确认，醛固酮拮抗剂、     

局部肾素-血管紧张素-醛固酮系统与糖尿病肾病的治疗

循环中肾素-血管紧张素-醛固酮系统(RAAS)成分由分布于全身的组织细胞合成与分泌.糖尿时,肾脏局部肾素、血管紧张素(Ang)Ⅱ、醛固酮等活性增加,它们作用于血管或通过激活炎症因子等途径,导致肾血管病变及肾纤维化.动物试验与临床研究表明,抑制RAAS可延缓糖尿病肾病进程.     

肾血管性高血压和肾上腺腺瘤患者肾素-血管紧张素-醛固酮含量分析

目的 探讨肾素-血管紧张素-醛固酮系统、内皮素、一氧化氮在肾血管性高血压患者、肾上腺腺瘤患者中的作用和意义.方法 采用放射免疫分析的方法测量肾血管性高血压组(40例)、肾上腺腺瘤组(35例)和健康对照组(35例)血清肾素、血管紧张素Ⅱ、醛固酮、内皮素含量,用酶免疫法测定上述人群一氧化氮合酶(NOS)的含量来表示NO的量.结果 肾血管性高血压患者肾素、血管紧张素、醛固酮、内皮素含量高于健康对照组(P＜0.01),NOS含量低于健康对照组(P＜0.05);肾上腺腺瘤组醛固酮和内皮素含量高于健康对照组(P＜0.01),肾素、血管紧张素低于健康对照组(P＜0.05).结论 肾索、血管紧张素、醛固酮、内皮素和NO的检测可为临床早期诊断肾上腺腺瘤、肾血管性高血压提供依据.     

肾素-血管紧张素系统抑制剂治疗心力衰竭的循证依据

肾素-血管紧张素系统(renin-angiotensin system,RAS)抑制剂在心力衰竭治疗中具有不可替代的地位。本文简述RAS抑制剂的作用机制、分类和临床应用,着重回顾RAS抑制剂用于治疗心力衰竭的各项重要临床试验结果。现有的临床证据表明,血管紧张素转化酶抑制剂仍是心力衰竭治疗的"基石",其地位尚无其他RAS抑制剂能够替代。对血管紧张素转化酶抑制剂不能耐受时可以血管紧张素Ⅱ受体拮抗剂替代,但目前没有足够的证据支持这两类药物联合用药治疗心力衰竭。肾素抑制剂是一类新药,至今还无临床证据支持其用于心力衰竭治疗,且不良反应也值得关注。     

Blockade of the renin-angiotensin-aldosterone system: effects on hypertensive target organ damage

The renin-angiotensin-aldosterone system (RAAS) plays a relevant role not only in the pathophysiology of essential hypertension, but also in the development of hypertensive target organ damage. Different drugs acting on RAAS components are now available: angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II AT1 receptors blockers (ARBs), non-selective and selective aldosterone antagonists. The review will focus on their effects on hypertensive organ damage. In fact, apart from the well known efficacy in reducing blood pressure, all these drugs have been demonstrated to protect against target organ damage, reversing or preventing its development. The main issues addressed will be: effects of the RAAS blockade on heart and kidney disease, protective action against arterial wall damage, with a focus on the endothelial protection. The comparison among ACE inhibitors, ARBs and aldosterone antagonists will be discussed, with specific reference to different class and/or drug effects and to the results of few studies evaluating the effects of combination therapy with different drugs blocking the RAAS.     

Combinations of renin-angiotensin-aldosterone system antagonists: true advantages?

The renin angiotensin aldosterone system (RAAS) inhibitors induce an incomplete blockade of the system at different steps. Recently, the dual RAAS therapy is emerging in clinical practice, although there is a lack of evidence on safety and efficacy for this combination in several cardiovascular diseases. In this review, we evaluated the advantages and disadvantages of dual RAAS blockade in hypertension, proteinuric renal disease, heart failure and ischaemic heart disease. The role of DRIs in combination with ACEI or ARBs is promising, but still needs further studies. On the basis of the clinical outcomes and safety data the recommendations guidelines have not confirmed indications to dual RAAS blockade in essential hypertension treatment, heart failure and ischemic heart disease. Only proteinuric nephropathies and resistant hypertension may represent possible indications to dual RAAS blockade. Actually, rational combinations of either an ACEI or ARB or DRI with other classes of antihypertensives offer best solutions.     

Which antihypertensive drugs are the most nephroprotective and why?

Importance of the field: Hypertension is a major independent risk factor for kidney disease and for faster renal function loss. Choice of antihypertensive strategies with highest nephroprotective effect is crucial to prevent or reverse progression to end stage renal disease (ESRD).

Areas covered in this review: The present review focuses on the role of hypertension in the progression of chronic kidney disease (CKD), the renoprotective effects of different antihypertensive therapies, and the blood pressure levels that should be targeted in different patient populations. To this end, the PubMed (1975 – 2010) database was searched for English-language articles, using the following keywords: hypertension, kidney disease, ACE-inhibitor, angiotensin receptor blocker, aldosterone antagonist, renin inhibitor, proteinuria.

What the reader will gain: A comprehensive review of data on the association between hypertension and progression of chronic nephropathies and on the antihypertensive treatments with highest nephroprotective effects.

Take home message: Blood pressure should be targeted to 140/90 mmHg or less in patients with hypertension but no renal injury and 130/80 mmHg or less in those with CKD. Amongst different antihypertensive drugs, renin angiotensin aldosterone system (RAAS) inhibitors have an incremental nephroprotective effect in proteinuric patients. Maximal RAAS inhibition should be aimed to optimize renoprotection in hypertensive patients with CKD and proteinuria.     

Combined neutral endopeptidase inhibitors

INTRODUCTION: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of hypertension and heart failure. ACE inhibitors, angiotensin receptor II blockers (AT-II blockers) and aldosterone antagonists have been used to tackle the RAAS in the past but combined ACE and neutral endopeptidase (NEP) inhibitors have been shown to be more potent in reducing blood and especially pulse pressure in patients with hypertension. AREAS COVERED: Different NEP inhibitors have been tested but omapatrilat is the most widely studied in the setting of hypertension, heart failure and chronic angina. We have undertaken a PubMed search on NEP with a special focus on omapatrilat and its efficacy in hypertension and heart failure. The incidence of angioedema is more frequent in patients taking combined ACE and NEP inhibitors and this has prevented these medications from finding a widespread use. Combinations of NEP inhibitors and AT-II blockers are currently being studied and have been shown to reduce the blood pressure significantly. These medications have so far not been associated with angioedema and have a great potential to be safe and effective alternatives in the near future. EXPERT OPINION: NEP inhibitors were effective in the treatment of hypertension and heart failure but the relatively high incidence of angioedema stopped their widespread use. New hope has risen with the introduction of combined NEP inhibitors and AT-II blockers and early studies are encouraging.     

RAAS抑制剂在对比剂致维吾尔族患者性肾损伤中的作用

摘要：目的 探讨对比剂致维吾尔族患者急性肾损伤（CI-AKI）发生率、危险因素及肾素-血管紧张素-醛固酮系 统（RAAS）抑制剂在其中是否发挥影响作用。方法 回顾性分析新疆维吾尔自治区和田地区人民医院心脏诊疗中 心成功行经皮冠状动脉介入治疗（PCI）手术，并于24～48 h后复查肾功能的218例维吾尔族患者的临床资料。按照 有无CI-AKI分为CI-AKI组（n=46）及对照组（n=172），观察2组患者一般资料，分析CI-AKI的危险因素及RAAS抑制 剂在其中的作用。结果 218例患者中发生CI-AKI 46例（21.1%）。CI-AKI组中高血压患病率、对比剂用量、低密度 脂蛋白胆固醇（LDL-C）水平、N末端B型脑钠肽前体（NT-proBNP）水平、高敏C反应蛋白（hs-CRP）水平高于对照组； RAAS抑制剂使用比例、左室射血分数（LVEF）水平、高密度脂蛋白胆固醇（HDL-C）水平、血红蛋白（HB）水平低于对 照组（P＜0.05）。CI-AKI组及对照组术前肌酐清除率差异无统计学意义。术前CI-AKI组肌酐水平低于对照组，但 术后CI-AKI组肌酐水平较术前明显增加（P＜0.05）。术前2组间尿素氮水平差异无统计学意义，但术后CI-AKI组尿 素氮水平明显增加。多因素Logistic分析发现对比剂用量增加、高NT-proBNP及hs-CRP水平仍为维吾尔族患者发 生CI-AKI的危险因素，使用RAAS抑制剂是保护因素。结论 对于维吾尔族拟行PCI治疗患者，术前使用RAAS抑 制剂，改善术前心功能，减少术中对比剂用量能够降低CI-AKI发生风险。     

Introduction

Systemic hypertension is a long-term risk factor for the development of atherosclerotic vascular disease and when uncontrolled is a short-term trigger of acute vascular events such as acute coronary syndromes and stroke. Thus, rapid reduction in BP is desirable. Patients at high risk for vascular disease, such as those with diabetes mellitus, have aggressive goal BP targets because studies have shown that achieving these targets reduces events. Given the dual goals in high-risk patients of reducing BP quickly and to aggressively low targets, the classic ‘step therapy’ of one drug titrated at a time to reduce BP is inadequate. Combination therapy with at least two potent medications makes more sense, and manufacturers are now increasing their offerings of single-pill combinations for hypertension. Combination pills are popular with patients and increase compliance with therapy. Many believe that renin-angiotensin aldosterone system (RAAS) blockers are the cornerstone of hypertension treatment in patients at high risk for vascular disease. The newer combination pills include a RAAS blocker and diuretics or a long-acting calcium channel antagonist (CCA). Recent studies have shown that a RAAS blocker plus a dihydropyridine CCA is superior to older diuretic-based combinations for preventing cardiovascular events. These considerations support a new approach to the higher risk hypertensive patient: effective doses of RAAS blocker/CCA combination pills to rapidly lower BP to <130/80 mmHg.     

Epidemiology and Management of Hypertension in the Hispanic Population

Hispanics are the fastest growing ethnic minority in the USA. Among Hispanics, lack of hypertension awareness and lack of effective blood pressure (BP) control are problematic, as are higher incidence rates of hypertension-related co-morbidities compared with non-Hispanic populations. Moreover, there are currently no hypertension treatment guidelines that address the unique characteristics of this ethnic group. This article discusses ethnic differences in hypertension and cardiovascular risk factors and reviews the literature on the efficacy of antihypertensive agents in Hispanic patients, with a focus on the role of renin-angiotensin-aldosterone system (RAAS) inhibition in the management of hypertension in these patients. Hypertension in Hispanic patients can be challenging to manage, in part because this population has a higher prevalence of obesity, diabetes, and metabolic syndrome compared with non-Hispanic whites. The presence of these co-morbidities suggests that RAAS-inhibitor-based therapies may be particularly beneficial in this population. However, few studies have evaluated the efficacy of antihypertensive treatments in Hispanic patients. Two outcomes studies in hypertensive patients have shown the benefits of treating Hispanic patients with antihypertensive therapy and included RAAS inhibitors as part of the treatment regimen. In addition, BP-lowering trials have shown the antihypertensive efficacy of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and direct renin inhibitors, although data on the latter are more limited. Additional studies are needed to more thoroughly evaluate the effects of RAAS inhibitors (and other drug classes) on outcomes and BP lowering in the Hispanic hypertensive population.     

The renin inhibitor aliskiren as novel treatment for cardiovascular disease

The renin-angiotensin aldosterone system (RAAS) plays a key role in the regulation of blood pressure, acting via the effects of the hormone angiotensin (Ang) II. Ang II increases blood pressure and can exert growth-promoting effects leading to end-organ damage. Excess RAAS activity has been shown to be a major underlying cause of hypertension, heart failure, and related cardiovascular disorders. Inhibitors of renin block the RAAS at its first and rate-limiting step and thus appear to offer an excellent opportunity for blood pressure control. In the past two decades various potential renin inhibitors have been developed but have not been clinically useful. This review discusses a recent patent in the development of a novel class of non-peptide renin inhibitors: an alkanecarboxamide, aliskiren (SPP-100; Novartis). Aliskiren is effective in animal models, while recent results from studies in humans indicate that aliskiren is the first in a new class of orally effective renin inhibitors for the treatment of hypertension.     

Aliskiren: beyond blood pressure reduction

Importance of the field: Hypertension is one of the most important risk factors and causes of cardiovascular disease (CVD). From some years, renin-angiotensin-aldosterone system (RAAS) inhibitors such angiotensin converting enzyme (ACE) and angiotensin receptor blockade (ARB) have been of interest, not only for better blood pressure (BP) control but also for their involvement in the mechanisms of various organ functions.

Areas covered in this review: The aim of this review is to focus on the effectiveness and safety of aliskiren beyond the treatment of hypertension.

What the reader will gain: Aliskiren, the first approved renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks angiotensin I generation. Because of its mechanism of action, aliskiren may offer the additional opportunity to inhibit progression of atherosclerosis at tissue level and the potential to be useful in a wide spectrum of conditions. However, we will discuss how it might become a reasonable therapeutic choice also in a broad number of clinical conditions, sharing an increased cardiovascular risk as stable coronary artery disease (CAD), microvascular and cardio-renal disease, diabetes, and peripheral arterial disease (PAD).

Take home message: Therapy of hypertension through a better blockade of RAAS may be the first step in also achieving interesting results in the complications that hypertension causes in several organs.