转化酶抑制剂在严重充血性心力衰竭病人中的持久作用

在严重失代偿性心力衰竭时,肾素-血管紧张素-醛固酮系统可被激活,这些患者的体循环血管阻力增高可能是与血管紧张素增高有关。为此,临床上曾有在严重充血性心力衰竭中应用肾素-血管紧张素-醛固酮系统阻断剂的报道。本文报告应用口服转化酶抑制剂巯甲丙脯氨酸(Captopril)治疗严重充血性心力衰竭的长期效果。     

肾素-血管紧张素-醛固酮系统抑制与心房颤动

心房颤动(房颤)是临床最常见的心律失常之一,大多数房颤复律后容易反复发作,部分转为永久性房颤。积极地控制房颤,不仅在于消除患者心悸等不适症状,而且对防止血栓栓塞等并发症的发生有重要意义。近年来,大量研究显示通过抑制肾素-血管紧张素-醛固酮系统可对房颤有一定的预防作用。因此,应用血管紧张素转换酶抑制剂和血管紧张素受体阻断剂抑制肾素-血管紧张素-醛固酮系统预防房颤,可望成为控制房颤的一条新途径。     

血浆肾素、血管紧张素II和醛固酮与肝纤维化关系的实验研究

肾素-血管紧张素-醛固酮系统（RAAS）是机体调节血管张力和钠水代谢的内分泌系统。肝硬化患者常有。肾素-血管紧张素系统活性增高和醛固酮增多，一般认为系肝脏对醛固酮的灭活减少等引起的。但近年来的研究表明，多种器官和组织都能合成肾素和血管紧张素系统的成分，参与器官纤维化。肝脏也存在局部肾素．血管紧张素系统。为深入了解血浆肾素、血管紧张素和醛固酮水平与肝纤维化的关系。     

年龄与肾素-血管紧张素-醛固酮系统及血压的研究进展

近年来对于肾素-血管紧张素-醛固酮系统的研究逐渐增多,现对肾素-血管紧张素-醛固酮系统与年龄之间关系的研究进展作一综述.     

肾素-血管紧张素系统阻断剂与心房颤动

心房颤动是临床最常见的心律失常之一,发病率呈增加趋势。心房电重构和结构重构是心房颤动维持和复发的主要机制,肾素-血管紧张素系统在心房重构中起重要作用。肾素-血管紧张素系统阻断剂（血管紧张素转化酶抑制剂和血管紧张素受体阻断剂）通过抑制心房不应期缩短和抗心房结构重构等作用抑制心房重构并减少心房颤动的发作。肾素-血管紧张素系统阻断剂影响心房结构和功能,为心房颤动的防治提供了一种新的选择。     

血浆肾素、血管紧张素Ⅱ和醛固酮与肝纤维化关系的实验研究

肾素-血管紧张素-醛固酮系统(RAAS)是机体调节血管张力和钠水代谢的内分泌系统.肝硬化患者常有肾素-血管紧张素系统活性增高和醛固酮增多,一般认为系肝脏对醛固酮的灭活减少等引起的.     

肝星形细胞存在局部肾素-血管紧张素-醛固酮系统

目的 明确肝星形细胞和永生肝星形细胞株HSC-T6是否存在局部肾素-血管紧张素-醛固酮系统。方法 采用原位酶灌注法分离培养肝星形细胞。采用放射免疫法检测细胞中肾素活性，血管紧张素Ⅱ和醛固酮水平；采用紫外分光光度法测定血管紧张素转换酶活性，免疫组化法检测血管紧张素Ⅱ1型受体的表达；RT-PCR法检测肾素，血管紧张素原，血管紧张素转换酶，血管紧张素Ⅱ1型受体醛固酮合成关键酶CYPⅡB2mRNA的表达。结果 肝星形细胞和HSC-T6中可检测到肾素活性，血管紧张素转换酶活性，血管紧张素Ⅱ和醛固酮；免疫组化结果显示二者均表达血管紧张素Ⅱ的1型受体；两种细胞均可检测到上述除血管紧张素原以外的4种基因mRNA表达。结论 肝星形细胞和HSC-T6存在局部肾素-血管紧张素-醛固酮系统。     

肾素-血管紧张素-醛固酮系统对血压昼夜节律的影响

肾素-血管紧张素-醛固酮系统在血压昼夜节律的调节中起着关键作用。现综述近年来肾素-血管紧张素-醛固酮系统昼夜节律的机制及其对血压影响的研究进展。     

高血压伴焦虑抑郁症与肾素-血管紧张素-醛固酮系统研究新进展

研究发现,高血压伴焦虑抑郁症与肾素-血管紧张素-醛固酮系统密切相关,现就高血压、焦虑抑郁症与肾素-血管紧张素-醛固酮之间的关系做一综述。     

利尿钠肽及肾素-血管紧张素-醛固酮系统对高血压的影响

正高血压是最常见的心血管疾病之一,是脑卒中、冠状动脉粥样硬化性心脏病(冠心病)的重要危险因素~([1])。高血压的发病机制复杂多样,除遗传及环境因素外,体液因素也发挥着重要作用,包括肾素-血管紧张素-醛固酮系统(RAAS)、激肽-前列腺素系统、儿茶酚胺及血管内皮舒缩因子等~([2]),深入了解体液因素与高血压的关系,给予针对性干预,有着重要意义。1肾素-血管紧张素-醛固酮系统(RAAS)肾素、血管紧张素、醛固酮存在于血液及局部组织发挥     

New roles for renin and prorenin in heart failure and cardiorenal crosstalk

The renin-angiotensin-aldosterone-system (RAAS) plays a central role in the pathophysiology of heart failure and cardiorenal interaction. Drugs interfering in the RAAS form the pillars in treatment of heart failure and cardiorenal syndrome. Although RAAS inhibitors improve prognosis, heart failure–associated morbidity and mortality remain high, especially in the presence of kidney disease. The effect of RAAS blockade may be limited due to the loss of an inhibitory feedback of angiotensin II on renin production. The subsequent increase in prorenin and renin may activate several alternative pathways. These include the recently discovered (pro-) renin receptor, angiotensin II escape via chymase and cathepsin, and the formation of various angiotensin subforms upstream from the blockade, including angiotensin 1–7, angiotensin III, and angiotensin IV. Recently, the direct renin inhibitor aliskiren has been proven effective in reducing plasma renin activity (PRA) and appears to provide additional (tissue) RAAS blockade on top of angiotensin-converting enzyme and angiotensin receptor blockers, underscoring the important role of renin, even (or more so) under adequate RAAS blockade. Reducing PRA however occurs at the expense of an increase plasma renin concentration (PRC). PRC may exert direct effects independent of PRA through the recently discovered (pro-) renin receptor. Additional novel possibilities to interfere in the RAAS, for instance using vitamin D receptor activation, as well as the increased knowledge on alternative pathways, have revived the question on how ideal RAAS-guided therapy should be implemented. Renin and prorenin are pivotal since these are at the base of all of these pathways.     

Clinical Impact of Renin-Angiotensin System Blockade: Angiotensin-Converting Enzyme Inhibitors vs. Angiotensin Receptor Antagonists

Clinical trials have proved that blockade of the renin-angiotensin-aldosterone system (RAAS) offers primary and secondary protection of the cardiovascular system, brain, and kidneys. Drugs that interrupt the RAAS do so by several diverse mechanisms but it remains to be fully proved whether these mechanistic differences are associated with meaningful differences in clinical outcomes. This review summarizes current information about the basic mechanisms of action of three classes of anti-RAAS drugs: angiotensin-converting enzyme (ACE) inhibitors, combined ACE-neutral endopeptidase inhibitors, and angiotensin receptor antagonists as well as results of major clinical outcome trials with these agents. Basic and clinical science information is then blended with insights from the clinical pharmacology of anti-RAAS drugs to address four current controversies in clinical medicine: whether ACE inhibitors and angiotensin receptor antagonists are interchangeable, optimal dosing of available agents, potential justification of ACE inhibitor/angiotensin receptor antagonist combinations, and first-line use of anti-RAAS drugs in antihypertensive therapy.     

Clinical Impact of Renin-Angiotensin System Blockade: Angiotensin-Converting Enzyme Inhibitors vs. Angiotensin Receptor Antagonists

Clinical trials have proved that blockade of the renin-angiotensin-aldosterone system (RAAS) offers primary and secondary protection of the cardiovascular system, brain, and kidneys. Drugs that interrupt the RAAS do so by several diverse mechanisms but it remains to be fully proved whether these mechanistic differences are associated with meaningful differences in clinical outcomes. This review summarizes current information about the basic mechanisms of action of three classes of anti-RAAS drugs: angiotensin-converting enzyme (ACE) inhibitors, combined ACE-neutral endopeptidase inhibitors, and angiotensin receptor antagonists as well as results of major clinical outcome trials with these agents. Basic and clinical science information is then blended with insights from the clinical pharmacology of anti-RAAS drugs to address four current controversies in clinical medicine: whether ACE inhibitors and angiotensin receptor antagonists are interchangeable, optimal dosing of available agents, potential justification of ACE inhibitor/angiotensin receptor antagonist combinations, and first-line use of anti-RAAS drugs in antihypertensive therapy.     

Reducing cardiorenal risk through combination therapy with a direct renin inhibitor

Interruption of the renin-angiotensin-aldosterone system (RAAS) cascade with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or more recently direct renin inhibitors (DRIs) is a safe and effective antihypertensive strategy that is in routine clinical use. The clinical utility of these agents in cardiorenal end-organ protection is increasingly being recognized. Although both ACE inhibitors and ARBs demonstrate substantial benefit in patients with cardiovascular and/or renal disease, considerable evidence indicates that they only partially suppress the RAAS pathway due to feedback upregulation of plasma renin activity. With the goal of providing more comprehensive RAAS blockade, combination ACE inhibitor/ARB therapy has been evaluated. However, this approach has not shown the anticipated improvements in composite cardiovascular and renal outcomes and appears to be associated with significant toxicity. Due to a unique mechanism of action, the combination of a DRI with an ACE inhibitor or ARB may represent an effective end-organ-protective therapeutic strategy.     

The renin-angiotensin-aldosterone system as a target in coronary disease

The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the development of atherosclerosis and adverse cardiovascular events. Traditionally, the pathologic effects of the RAAS were assumed to result from vasoconstriction induced by angiotensin II, and salt and water retention due to aldosterone. However, these hormones also have powerful trophic effects, stimulating increased mass in both the arterial wall and left ventricle. In addition, angiotensin II and aldosterone predispose to vascular inflammation, thrombosis, oxidative stress, and sudden cardiac death. Therapy directed at RAAS overactivity is essential for normalizing the prognosis of most patients with atherosclerosis. An angiotensin-converting enzyme (ACE) inhibitor improves the prognosis of patients with atherosclerosis and/or diabetes even in the setting of normal baseline blood pressure. Angiotensin receptor blocking agents also improve cardiovascular structure and prognosis. Although these agents are better tolerated than ACE inhibitors, they do not appear to be as effective in reducing event rates. Aldosterone receptor blocking agents also improve cardiovascular structure, function, and prognosis. Aldosterone receptor blockers appear to provide additive benefit when used in conjunction with either an ACE inhibitor or an angiotensin receptor blocker.     

The role of ACE inhibitors and angiotensin receptor blockers in the treatment of hypertension and cardiovascular disease

Pharmacologic attenuation of the renin-angiotensin-aldosterone system (RAAS) either through angiotensin-converting enzyme (ACE) inhibition or angiotensin II receptor blockade now occupies a central role in the management of hypertension, diabetes, heart failure, and cardiovascular and renal disease. Although our understanding and use of these agents has expanded significantly over the past decade, the relative and differential benefits of ACE inhibitors and angiotensin receptor blockers (ARBs) are still not entirely clear. The data continue to support the first-line use of ACE inhibitors for all indications. Results for combination ACE inhibitor and ARB therapy in clinical outcome trials have been disappointing and do not support its use. New strategies for RAAS modulation bring hope for further progress in the treatment of hypertensive and cardiovascular disease.     

It is Time to Reconsider the Cardiovascular Protection Afforded by RAAS Blockade - Overview of RAAS Systems

More than a century has passed since the renin-angiotensin-aldosterone system (RAAS) was discovered in 1897. Both circulatory and tissue RAAS have been found to be essential for regulation of the functions of the whole body, organs, tissues and cells. There is no doubt that the RAAS plays fundamental physiological roles in maintaining homeostasis, but it can also contribute to organ pathophysiology and tissue damages in some situations. Today, the usefulness of RAAS blockade is well-established in the management of a variety of cardiovascular disorders worldwide. However, the latest findings in this field are still providing us with new and unexpected insights into the pathophysiology of cardiovascular diseases. Such developments include dual blockade therapy with angiotensin I converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), and a new class of RAAS blockers, renin inhibitors. These give us the opportunity to revisit the basic principles of the RAAS and reconsider the strategies of RAAS blockade for cardiovascular protection.     

Potential benefits of aliskiren beyond blood pressure reduction

There is now clear evidence that reducing blood pressure (BP) with a broad range of agents, including angiotensin converting enzyme inhibitors and angiotensin receptor blockers, improves cardiovascular and renal outcomes. There is also evidence suggesting that these drugs have beneficial effects that are independent of BP lowering. Aliskiren is a direct renin inhibitor that interrupts the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step. Unlike angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, aliskiren produces a sustained reduction in plasma renin activity and reduces plasma levels of angiotensin II and aldosterone. Preclinical data and clinical trials in high-risk patients using surrogate markers increasingly suggest that aliskiren can reduce the progression of end-organ damage beyond that afforded by BP control. With its unique mechanism of action, combining aliskiren with another RAAS-blocking agent that has a different mechanism of action may provide more comprehensive blockade of the RAAS, potentially conferring additional clinical benefits. Evaluation of these end-organ effects in humans is underway in clinical trials designed to assess the effects of aliskiren alone and in combination with other antihypertensive agents on cardiovascular and renal outcomes.     

Direct renin inhibition: An update

Aliskiren, the first orally effective direct renin inhibitor, is an effective antihypertensive agent with distinctive properties including placebo-like tolerability, pharmacologic effects that persist after drug discontinuation, and a unique mechanism of action. When combined with agents that inhibit the reninangiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or β-blockers, additional blood pressure reduction reflects more complete RAAS blockade. Concern that marked elevation in plasma renin concentration following aliskiren administration might lead to RAAS-induced paradoxical blood pressure increases appears unfounded, based upon analyses of patients participating in clinical trials. Studies in animals and humans indicate that aliskiren accumulates in renal tissue, blocks the intrarenal RAAS, and interferes with deleterious cellular effects of angiotensin II by mechanisms that may include enzymatic blockade of renin and prorenin at the site of the (pro)renin receptor. In patients with diabetic nephropathy, adding aliskiren to losartan resulted in an additional 20% reduction in urinary protein excretion. In patients with heart failure, aliskiren reduced brain natriuretic peptide levels when added to other RAAS inhibitors, suggesting an additional hemodynamic effect. The ASPIRE HIGHER clinical trials program is assessing whether the promising pharmacologic properties of aliskiren translate into long-term clinical benefits.