药品信息

抗高血压药依普利酮 (eplerenone) 　 是一种新型选择性醛固酮受体拮抗剂 ,能特异性地抑制醛固酮功能。醛固酮是肾素 血管紧张肽 醛固酮系统中一种重要的成分 ,在调节人体心血管系统功能时发挥着重要作用 ,血管紧张肽转化酶抑制剂 (ACEI)和血管紧张肽Ⅱ受体拮抗剂 (ARB)可以抑制肾上腺分泌醛固酮 ,但经过一段时间治疗后 ,醛固酮的释放量有所恢复 ,其血浆浓度甚至可能超过基线水平。因此 ,有必要采用醛固酮受体拮抗剂治疗高血压。动物实验表明 ,依普利酮对高血压、心功能衰竭、心肌梗死、肾脏疾病及动脉粥样硬化有一定治疗作用。临床研…     

替米沙坦苯那普利治疗轻中度高血压疗效比较

替米沙坦是国产血管紧张素Ⅱ(AT-Ⅱ)受体拮抗剂类的口服抗高血压药物,它在减少血管紧张素转换酶抑制剂最常见的干咳副作用的同时,阻断肾素-血管紧张素-醛固酮系统更完全.本文通过替米沙坦和苯那普利的对照研究,来评价替米沙坦的抗高血压的疗效.     

血管紧张素Ⅱ受体拮抗剂治疗高血压的研究进展

血管紧张素(AT)受体拮抗剂能够作用于肾素—血管紧张素—醛固酮系统(RAAS),在对于高血压的治疗上有着重要的作用。它通过调整血管平滑肌细胞、心肌细胞来增加血管阻力和引起左心室肥厚等,现就AT受体拮抗剂与高血压之间的关系进行分析。     

醛固酮抑制剂的研究与开发

按醛固酮受体拮抗剂和非甾体醛固酮合酶抑制剂,分类概述了醛固酮抑制剂的结构类型、生物活性及构效关系研究进展。人体醛固酮水平的升高会引起高血压,进而导致心肌纤维化和充血性心力衰竭,因此研究与开发具有高活性和选择性的醛固酮受体拮抗剂及醛固酮合酶抑制剂对于防治此类心血管疾病具有积极意义。     

肾素拮抗剂进展与临床应用评价

目的：肾素-血管紧张素-醛固酮系统是人体内重要的血压调节机制之一,对后两个环节的抑制而促成了血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体阻断剂、醛固酮拮抗剂的生产和应用,成为对抗高血压临床应用的一线药,而肾素拮抗剂的问世则为抗高血压药团队中增添了一朵奇葩。方法：通过对国内外近期文献的复习,对肾素拮抗剂阿利克仑进行评价。结果及结论：在大量的临床研究中,阿利克仑显示了良好效果和安全性,在控制血压的治疗上标志着一个新里程的开始。     

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、     

肾素-血管紧张素-醛固酮系统抑制剂多靶点干预治疗高血压的研究进展

肾素-血管紧张素-醛固酮系统(RAAS)是参与高血压发病和维持不可或缺的环节;RAAS抑制剂治疗高血压被临床广泛应用,其中主要包括直接肾素抑制剂、血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂.它们作用于RAAS不同靶点,对RAAS抑制剂有效性的影响及其临床应用地位和意义一直被人们所关注,因此对三者各靶点作用特点的进行总结,以揭示RAAS抑制剂多靶点干预的重要性和意义.     

新型抗高血压药物作用机制及临床应用

高血压是各种心血管疾病的第一危险因素,血压达标对降低脑卒中、冠心病等并发症的发病率非常重要。目前国内外对新型抗高血压药物的研发,以肾素抑制剂、血管肽酶抑制剂(VPI)、醛固酮受体拮抗剂和内皮素(ET)受体拮抗剂四类药物最为集中。     

螺内酯治疗心衰

螺内酯(spironolactone,商品名Aldactone),旧称安体舒通,系醛固酮受体拮抗剂,为临床常用之留钾利尿药,治疗水肿、高血压和高醛固酮症。     

醛固酮阻断剂依普利酮在心血管疾病中的作用

肾素-血管紧张素-醛固酮系统过度激活及高醛固酮血症对心血管系统均有损伤作用。血管紧张素转化酶(ACE)抑制剂和血管紧张素受体阻断剂(ARB)已被证实可有效降低血压和保护靶器官，减少心力衰竭的发病率和死亡率；但长期使用ACE抑制剂或ARB治疗后，血醛固酮浓度又会回到基线水平，即所谓“醛固酮逃逸”，因此降低了这些药物进一步的疗效。醛固酮受体拮抗剂螺内酯对心血管系统有显著的保护作用，但它的性激素相关副作用限制了其应用。新一代选择性醛固酮受体拮抗剂依普利酮为心血管疾病的治疗开辟了新的道路。     

Recent studies with eplerenone, a novel selective aldosterone receptor antagonist.

Activation of the renin-angiotensin-aldosterone system is associated with unsatisfactory outcomes in patients with hypertension and congestive heart failure, in that activation of this system is correlated strongly with both the incidence and extent of end-organ damage. Despite the availability of the angiotensin-converting enzyme inhibitors and the AT1 receptor antagonists, unblocked aldosterone levels remain an important risk factor for cardiovascular disease progression. New preclinical data generated over the past few years strongly support the hypothesis that aldosterone has important deleterious effects on the cardiovascular system independent of the classical action of this hormone on renal epithelial cells. The new selective aldosterone receptor antagonist eplerenone has been shown to produce significant cardioprotective effects in experimental models of cardiovascular disease. Early clinical testing suggests that eplerenone may have important therapeutic benefit in the treatment of hypertension and heart failure.     

Aberrant Rac1–mineralocorticoid receptor pathways in salt‐sensitive hypertension

相似文献   

Evaluation of the ASPIRANT trial

Several pathophysiological, clinical, and therapeutic features of resistant hypertension are far from being clearly defined. This is the case also for the efficacy of aldosterone receptor antagonists as an add-on treatment of resistant hypertension. The Addition of Spironolactone in Patients with Resistant Arterial Hypertension (ASPIRANT) trial evaluated, with a double-blind, placebo-controlled design, the effects of low-dose (25 mg/day) spironolactone as compared with placebo on clinic and ambulatory blood pressure in 117 resistant hypertensive obese patients, already under treatment with at least four antihypertensive drugs. The primary study endpoint was the achievement of a statistically significant difference in the systo-diastolic blood pressure reduction during the daytime period between the spironolactone-treated and the placebo-treated group. The results show that aldosterone blockade was associated with a significant reduction in clinic, 24-h and daytime systolic (but not in diastolic) blood pressure as compared with the placebo-treated group, the systo-diastolic blood pressure difference between the two treatment regimens amounting to 5.4/1.0 mmHg. Although a number of limitations weaken some of the study conclusions, ASPIRANT trial provides the first controlled evidence on the blood pressure-lowering effects of low-dose spironolactone in resistant hypertensive patients.     

New developments in the diagnosis and management of resistant hypertension

Arterial hypertension is a well-known disease with a worldwide high prevalence and impaired prognosis with respect to normotensive subjects, due to increased cardiovascular mortality and morbidity. Blood pressure levels over range can be successfully controlled with adequate treatment, but more than 10% of hypertensive people have their blood pressure uncontrolled despite a therapeutic regimen of 3 or more antihypertensive drugs. These patients, named to have resistant hypertension, have a worse cardiovascular prognosis than controlled hypertensive subjects. Twenty-four hour-ambulatory blood pressure monitoring (ABPM) reveals that at least one third of these patients have indeed white-coat resistant hypertension, a rather more benign entity. In view of this evidence, performance of 24 h-ABPM is mandatory and to document the occurrence of subclinical target organ damage in this population before the development of cardiovascular disease is needed. This would help the physician to more rigorously implement adequate measures to control hypertension. On the other hand, the definition itself of the disease implies that conventional pharmacological treatment is not effective enough for these patients to reach normal blood pressure values. To treat resistant hypertensives, recent reports pay attention to the need to recover traditional treatments--either non-pharmacologic such as strict sodium diet restriction or pharmacologic such as the use of aldosterone receptor blockers--or to implement those treatments that are novelties, such as renal sympathetic nervous system ablation or carotid barorreceptors stimulation. This review focuses on outlining the current evidence about the diagnostic confirmation of resistant hypertension, the need to characterize these patients through 24 h-ABPM, to identify the presence of subclinical target organ damage, and to deal with not only classical but also novel treatment approaches for blood pressure control.     

Eplerenone: a selective aldosterone receptor antagonist (SARA)

Aldosterone, the final product of the renin-angiotensin-aldosterone system (RAAS), is a mineralocorticoid hormone that classically acts, via the mineralocorticoid (aldosterone) receptor, on epithelia of the kidneys, colon, and sweat glands to maintain electrolyte homeostasis. Aldosterone has also been shown to act at nonepithelial sites where it can contribute to cardiovascular disease such as hypertension, stroke, malignant nephrosclerosis, cardiac fibrosis, ventricular hypertrophy, and myocardial necrosis. Although angiotensin-converting enzyme (ACE) inhibitors and angiotensin type 1 (AT(1)) receptor antagonists act to suppress the RAAS, these agents do not adequately control plasma aldosterone levels--a phenomenon termed "aldosterone synthesis escape." Spironolactone, a nonselective aldosterone receptor antagonist, is an effective agent to suppress the actions of aldosterone; its use is, however, associated with progestational and antiandrogenic side effects due to its promiscuous binding to other steroid receptors. For these reasons, eplerenone--the first agent of a new class of drugs known as the selective aldosterone receptor antagonists (SARAs)--is under development. In rodent models, eplerenone provides marked protection against vascular injury in the kidney and heart. In phase II clinical trials, eplerenone demonstrates 24-h control of blood pressure with once or twice daily dosing, and is safe and well tolerated in patients with heart failure when given with standard of care agents. Pharmacokinetic studies reveal that eplerenone has good bioavailability with low protein binding, good plasma exposure, and is highly metabolized to inactive metabolites and excreted principally in the bile. Eplerenone is well tolerated in acute and chronic safety pharmacology studies. Ongoing phase III trials of eplerenone in the treatment of hypertension and heart failure are underway. These studies will extend our understanding of selective aldosterone receptor antagonism in the treatment of chronic cardiovascular disease.     

Correction of aldosterone level as marker of RAAS dysfunction in patients with arterial hypertension degree II-III and chronic kidney diseases

The hyperactivation of renin-angiotensin-aldosterone system (RAAS) underlies the development and the progression of arterial hypertension and chronic kidney diseases. Aldosterone is the main unit of RAAS and self-sufficient predictor of the development of cardiovascular events. In this study, the angiotensin receptor blocker valsartan, ACE inhibitor enalapril, and direct renin inhibitor aliskiren were used for the correction of blood pressure and aldosterone levels in patients with hypertension and chronic kidney diseases. The data obtained suggest that the proposed complex therapy provides the most complete blood pressure reduction and aldosterone level correction (as evidence of RAAS activity recovery), greatly improves the prognoses, and ensures maximum nephroprotection in the patients with arterial hypertension and chronic kidney diseases.     

Primary hyperaldosteronism due to adrenal microadenoma: a curable cause of refractory hypertension.

The diagnosis of primary hyperaldosteronism due to microadenoma or unilateral adrenal hyperplasia can be challenging, since hypokalaemic alkalosis, high plasma aldosterone and a definite adenoma on imaging may all be absent. METHOD AND RESULT: We describe three cases of resistant hypertension (on > or = 5 antihypertensives) where hyperaldosteronism was suspected because of a suppressed plasma renin level despite treatment with multiple drugs which normally elevate renin. Renin mass was measured by a double-site chemi-immunoluminometric assay. All patients had normal plasma aldosterone levels. Hypokalaemia was present in the first two cases but computed tomography did not show clear cut adenomas. Adrenal vein sampling (AVS) revealed lateralisation (> 4 times higher aldosterone to cortisol ratio (ACR) on the affected than contra-lateral side). The third patient was normokalaemic and AVS showed only minimal lateralisation (ACR 1.3:1). The severe hypertension in all cases was reversed by adrenalectomy, with blood pressure falling to target despite withdrawal of all but one to two drugs. CONCLUSIONS: The robotic assay of renin mass permits rapid detection of patients in whom plasma renin is suppressed below the normal range. A suppressed plasma renin indicates abnormal Na+-retention, and--when not overcome by drugs such as angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers--may be the only clue to a curable adrenal adenoma. AVS is required to demonstrate lateralisation of aldosterone secretion, justifying adrenalectomy.     

Aldosterone affects blood flow and vascular tone regulated by endothelium-derived NO: therapeutic implications

Aldosterone, in doses inappropriate to the salt status, plays an important role in the development of cardiovascular injury, including endothelial dysfunction, independent of its hypertensive effects. Acute non-genomic effects of aldosterone acting on mineralocorticoid receptors are inconsistent in healthy humans: vasoconstriction or forearm blood flow decrease via endothelial dysfunction, vasodilatation mediated by increased NO actions, or no effects. However, in studies with experimental animals, aldosterone mostly enhances vasodilatation mediated by endothelium-derived NO. Chronic exposure to aldosterone, which induces genomic responses, results in impairments of endothelial function through decreased NO synthesis and action in healthy individuals, experimental animals and isolated endothelial cells. Chronic aldosterone reduces NO release from isolated human endothelial cells only when extracellular sodium is raised. Oxidative stress is involved in the impairment of endothelial function by promoting NO degradation. Aldosterone liberates endothelin-1 (ET-1) from endothelial cells, which elicits ET_A receptor–mediated vasoconstriction by inhibiting endothelial NO synthesis and action and through its own direct vasoconstrictor action. Ca²⁺ flux through T-type Ca²⁺ channels activates aldosterone synthesis and thus enhances unwanted effects of aldosterone on the endothelium. Mineralocorticoid receptor inhibitors, ET_A receptor antagonists and T-type Ca²+ channel blockers appear to diminish the pathophysiological participation of aldosterone in cardiovascular disease and exert beneficial actions on bioavailability of endothelium-derived NO, particularly in resistant hypertension and aldosteronism.