血管紧张素转换酶抑制剂对心力衰竭患者细胞因子干预作用的研究进展

充血性心力衰竭（congestive heart failure,CHF）是多种心血管疾病所致的一种临床综合征,其病理生理机制除交感神经系统（sympathetic nervous system,SNS）和肾素-血管紧张素-醛固酮系统（rennin-angiotensin-aldosterone system,RAAS）的激活外,细胞因子的激活和失衡也参与了CHF的发生发展过程。有研究证实,血管紧张素转换酶抑制剂（angiotensin convertingenzyme inhibiter,ACEI）不但能阻断SNS及RAAS的激活,还能调整细胞因子网络的失衡,逆转心室肥厚以及防止和延缓心室重构,有助于延缓、遏止CHF进展。本文总结了ACEI对CHF患者血清炎症细胞因子的干预作用的研究现状,探讨通过此途径治疗CHF的效果。     

Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Prothrombotic Processes and Myocardial Infarction Risk

Acute ischemic events occur most frequently at dawn and in the early hours of the morning. The development of these severe clinical events exhibits a temporal relationship with changes in various hemodynamic, prothrombotic, and hormonal processes. The authors highlight not only these relationships but also the potential protective effect of increased bradykinin levels and the inhibition of different angiotensin II (AT-II) receptors (AT2, AT4) against unfavorable prothrombotic influences, which—based on studies to date—decreases the risk of acute cardiovascular events. Comparisons are presented between the different effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on factors that influence thrombus formation and myocardial infarction risk.     

血管紧张素转换酶抑制剂的临床应用

血管紧张素转换酶抑制剂是治疗心血管疾病，特别是高血压和心力衰竭的重要药物。该类药物发展快、品种多，可按化学结构、药代动力学及作用时间长短分为不同的种类；临床应用的领域也在不断地被拓展，从降压、治疗慢性收缩性心力衰竭，到保护缺血性心肌，展示了其广阔的发展前景。在临床应用中要掌握其用法和禁忌证，改变“小剂量与大剂量同样有效，小剂量可减少副作用”的观点，宜与相应药物联用，以避免不良反应的发生，增强药效。     

急性心肌梗死患者血管紧张素转化酶抑制剂和血管紧张素受体阻滞剂的应用及影响因素

目的 了解天津市静海区急性心肌梗死(AMI)患者中血管紧张素转化酶抑制剂和血管紧张素受体阻滞剂(ACEI/ARB)的使用情况,并探讨其影响因素.方法 通过调查天津市静海区医院2001、2006、2011三个特定年份的研究病历,分析ACEI/ARB的使用情况,并采用二元lo-gistic回归方法 探讨其使用的影响因素.结果 共入选598例患者,其中中国指南Ⅰ类推荐组589例,指南Ⅱa类推荐组9例.2001年、2006年和2011年,指南Ⅰ类推荐患者ACEI/ARB使用率分别为69.86%、64.11%和69.97%(P>0.05),2001年、2006年和2011年指南Ⅱa类推荐患者为32.65%、33.33%和50.00%(P>0.05).ACEI/ARB使用率随时间推移呈小幅提高.在3个研究年份中,ACEIs使用率均显著高于ARBs.多因素分析显示,与对应组相比合并高血压(OR 2.20,95%CI 1.50~3.30)、心力衰竭(OR 1.70,95%CI 1.20~2.60)的患者更倾向于使用ACEI/ARB,相反,合并eGFR<60mL/(min·1.73m2)的患者较少使用ACEI/ARB(OR 0.30,95%CI 0.20~0.70).结论 约三分之一静海区急性心肌梗死Ⅰ类推荐患者住院期间未接受ACEI/ARB治疗,随时间推移呈小幅提高.     

Differences in the Clinical Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: A Critical Review of the Evidence

The renin–angiotensin–aldosterone system plays a major role in the pathophysiology of hypertension and closely related cardio- and cerebrovascular events. Although both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) are equally important in the treatment of hypertension, according to the results of recent years, there might be substantial differences in their cardiovascular protective effects, and these differences might be explained by our increasing knowledge of their non-overlapping mechanisms of action. The number of studies investigating how ACE inhibitors and ARB agents differ will certainly be increasing in the future. ACE inhibitors are the safe therapeutic opportunity for hypertensive patients at high risk, with a cardiological comorbidity.     

The Use of Angiotensin-Converting Enzyme Inhibitors After Acute Myocardial Infarction

During and immediately after myocardial infarction (MI), many interrelated and complex processes manifest the body's attempt to minimize damage and compensate for lost cardiac function. Although these compensatory responses may provide some short-term restoration of function, their long-term consequences actually may increase morbidity and mortality. Several agents have established roles in the treatment of these patients, whereas others, including the angiotensin-converting enzyme (ACE) inhibitors, have yet to be investigated thoroughly. Results of two trials investigating the role of ACE inhibition after MI seem to provide sufficient data to warrant the use of these drugs in certain patient populations. These results are promising, but further investigation is necessary to answer key questions arising from these trials.     

Relative Lipophilicities and Structural-Pharmacological Considerations of Various Angiotensin-Converting Enzyme (ACE) Inhibitors

Lipophilicities of seven structurally diverse angiotensin-converting enzyme (ACE) inhibitors, viz., captopril, zofenoprilat, enalaprilat, ramiprilat, lisinopril, fosinoprilat, and ceronapril (SQ29852), were compared by determining their octanol-water distribution coefficients (D) under physiological pH conditions. The distribution coefficients of zofenopril, enalapril, ramipril and fosinopril, which are the prodrug forms of zofenoprilat, enalaprilat, ramiprilat, and fosinoprilat, respectively, were also determined. Attempts were made to correlate lipophilicities with the reported data for oral absorption, protein binding, ACE inhibitory activity, propensity for biliary excretion, and penetration across the blood-brain barrier for these therapeutic entities. Better absorption of prodrugs compared to their respective active forms is in agreement with their greater lipophilicities. Captopril, lisinopril, and ceronapril are orally well absorbed despite their low lipophilicities, suggesting involvement of other factors such as a carrier-mediated transport process. Of all the compounds studied, the two most lipophilic ACE inhibitors, fosinoprilat and zofenoprilat, exhibit a rank-order correlation with respect to biliary excretion. This may explain the dual routes of elimination (renal and hepatic) observed with fosinoprilat in humans. The more lipophilic compounds also exhibit higher protein binding. Both the lipophilicity and a carrier-mediated process may be involved in penetration of some of these drugs into brain. For structurally similar compounds, in vitro ACE inhibitory activity increased with the increase in lipophilicity. However, no clear correlation between lipophilicity and ACE inhibitory activity emerged when different types of inhibitors are compared, possibly because their interactions with enzymes are primarily ionic in nature.     

Cardiovascular and Renal Review: Pharmacology of Angiotensin II Receptor Antagonists: Comparison with Renin Inhibitors and Angiotensin-Converting Enzyme Inhibitors

Nonpeptide angiotensin II (ANG II) receptor antagonists are a new class of inhibitors of the renin angiotensin system (RAS). Several ANG II receptor antagonists are currently in clinical development for the treatment of hypertension and heart failure. The discovery of these compounds follows many years of research on renin and the spectacular success of angiotensin converting enzyme (ACE) inhibitors, both as therapeutic agents and pharmacological tools. By inhibiting the interaction of ANG II with its receptor(s), studies utilising ANG II receptor antagonists have furthered our understanding of the RAS. This class of compounds may provide an interesting alternative to ACE inhibitors for the clinical management of hypertension and heart failure. The present article examines the comparative preclinical pharmacology of ANG II receptor antagonists, ACE inhibitors and renin inhibitors, with two objectives: 1) to demonstrate how our knowledge of the RAS has been extended utilising these three classes of pharmacological tools; and, 2) to review how ANG II receptor antagonists have been used in preclinical animal models with respect to their potential clinical indications.     

Delayed Onset of Angioedema with Angiotensin-Converting Enzyme Inhibitors: Case Report and Review of the Literature

The angiotensin-converting enzyme inhibitors have gained widespread application in the management of hypertension and congestive heart failure, and after myocardial infarction. They are generally considered safe drugs, but there are a number of reports of angioedema associated with their use. In general, angioedema occurs within hours to days after initiation of therapy, and only a limited number of reports document a delayed onset. Our patient experienced angioedema after 14 months of therapy with benazepril.     

Angiotensin-Converting Enzyme Inhibitors and Their Influence on Inflammation,Bronchial Reactivity and Cough

Drug Safety - Synthetic orally active angiotensin-converting enzyme (ACE) inhibitors have been successfully used in the treatment of congestive heart failure and hypertension, particularly in...     

Potential Angiotensin-Converting Enzyme Inhibitor—Epoetin Alfa Interaction in Patients Receiving Chronic Hemodialysis

We compared epoetin alfa (EPO) dose requirements and hematocrit response in 17 patients receiving chronic hemodialysis at baseline and after 3 and 12 months of therapy with angiotensin-converting enzyme (ACE) inhibitors (12 enalapril, 5 captopril). No acute processes were present (infection, hemorrhage, inflammation) at time of starting ACE inhibitor therapy. Mean (± SD) intravenous EPO dosages at zero, 3, and 12 months were 6012 ± 2575, 5800 ± 2026, and 5660 ± 2285 U 3 times/week (p=0.56), and mean differences were − 212 U for 0–3 months (95% CI −1310 to 886) and −713 U for 0–12 months (95% CI −2142 to 716). Mean ± SD hematocrits were 30.5 ± 3.9%, 31.6 ± 3.2%, and 34.2 ± 3.1% (p=0.01, zero vs 12 mo), and mean differences were 1.7% for 0–3 months (95% CI −1.41 to 4.81) and 3.85% for zero–12 months (95% CI 0.71–7). Our results indicate that ACE inhibitors do not increase EPO dose requirements or reduce hematocrits in these patients.     

2种钙通道阻滞剂和3种血管紧张素转换酶抑制剂的近期肾保护作用比较

目的：研究钙通道阻滞剂(CCBs)和血管紧张素转换酶抑制剂(ACEIs)肾保护作用的差别。方法：原发性肾小球疾病患者104例。随机、配对分为氨氯地平组17例；马尼地平组19例；卡托普利组21例；西拉普利组24例；依那普利组23例。分别投与这5种药治疗4个月。治疗前、治疗后1，2，3和4个月及停药后1个月检测平均动脉压(MAP)、尿蛋白、尿白蛋白排泄率(UAER)、肾功能、尿钠、尿尿素氮以及尿蛋白选择指数(UPSI)。结果：5组患者治疗期间蛋白和食盐摄入量以及UPSI均无明显变化，各组间比较无明显差别，5组患者治疗后MAP均明显降低，但各组间比较无明显差别；治疗后尿蛋白、UAER和肌酐清除率(cCr)，2个CCBs组比较均无明显变化，而3个ACEIs组均明显降低，但停药后恢复至治疗前水平，3组间比较无明显差别。结论：对原发性肾小球疾病患者，ACEIs有较好的近期肾保护作用，而CCBs效果不明显。     

Effect of Long-Term Angiotensin-Converting Enzyme Inhibitor Therapy on Arterial Oxygen Saturation in Patients With Mild to Moderate Heart Failure

Study Objective . To evaluate the effects of angiotensin-converting enzyme (ACE) inhibition on continuous pulse oximetry recordings of arterial oxygen saturation (SpO₂). Design . Open-label study. Setting . Cardiology clinics at two large teaching hospitals. Patients . Eight patients with New York Heart Association Functional Class (NYHA FC) II-III heart failure. Interventions . Patients were studied after an ACE inhibitor washout (baseline, B), and after 3 months following resumption of therapy (ACEI). Measurements and Main Results . Monitoring times for B and ACEI were approximately 22 hours. Reduction trends were observed for number (190 ± 170 vs 125 ± 67 B vs ACEI), magnitude (8.2 ± 1.4% vs 7.5 ± 1.8%), and duration (2.45 ± 2.8 vs 1.35 ± 0.8 min) of desaturations/monitoring period, and for nadir SpO₂/desaturation (88.1 ± 1.5% vs 89.9 ± 3.3%). The B desaturation index [(cumulative desaturation time/monitoring period time) × 100, a measure of hypoxic stress or burden] decreased from 19.4 ± 8.1% to 11.9 ± 8.1% at ACEI (p=0.024). Conclusion . Long-term ACE inhibitor therapy improves the profile of SpO₂ values over time in patients with NYHA FC II-III heart failure.     

ACE 2350 G/A基因多态性与高血压左心室肥厚的关系

目的:探讨血管紧张素转换酶(ACE)2350G/A基因多态性与原发性高血压及合并左心室肥厚(LVH)的关系。方法:利用聚合酶链反应(PCR)及限制性酶切技术对194例健康人(对照组)与246例原发性高血压病患者(高血压组)ACE2350G/A基因多态性进行检测;利用二维超声心动图对178例未治疗原发性高血压患者检测左心室质量(LVM),计算左心室质量指数(LVMI)。结果:高血压组与对照组的ACE2350G/A基因分型及等位基因的频率差别无统计学意义;但原发性高血压伴LVH组基因分型及等位基因的频率与非LVH组差别有统计学意义;左心室肥厚A等位基因的频率(58.09%)高于非左心室肥厚的频率(42.27%,P=0.0037)。结论:原发性高血压患者ACE2350A等位基因与左心室肥厚密切相关。     

伊贝沙坦(国产)与缬沙坦治疗轻、中度高血压病疗效观察——随机、双盲平行对照研究

目的通过伊贝沙坦(南京京华生物工程有限公司生产)与缬沙坦(北京诺华制药股份有限公司)的对比研究来评论伊贝沙坦(国产)对轻、中度原发性高血压病的降压疗效和安全性.方法53例轻、中度高血压病患者被随机、双盲分为两组,经口服安慰剂2周后,分别每日口服1次伊贝沙坦75～150mg(A组)或缬沙坦80～160mg(B组),治疗4周,观察用药前后坐位血压、心率变化,对比用药前后实验室检查,记录患者用药后的不良反应.结果治疗4周后,伊贝沙坦组舒张压降低13.3±8.7mmHg,缬沙坦组舒张压降低16.5±9.3mmHg.总有效率A组为76.0%,B组为84.0%.在药物的初始剂量下即能达到有效血压控制的患者数A组为72.0%,B组为68.0%.不良反应发生率A组为11.54%,B组为14.81%.两组患者治疗后与治疗前相比,血压下降有显著差异(P＜0.01),心率变化无显著差异(P＞0.05).降压幅度与总有效率两组间比较均无显著差异(P＞0.05).不良反应发生率两组间比较无显著差异(P＞0.05).结论口服伊贝沙坦75～150mg,每日1次,对轻、中度高血压病降压疗效确切,患者耐受性好.     

血管紧张素转换酶D等位基因与高血压性肾损害的探讨(附122例分析)

目的探讨血管紧张素转换酶(ACE)基因多态性是高血压病(EH)的致病基因,还是EH性肾损害的危险因素。方法四角分析法研究ACE基因多态性与EH的关系,采用PCR方法对比,有和无尿微量蛋白增高,EH组与对照组ACE多态性的差异。结果无论有还是没有EH家族史的EH组(n=122)和对照组(n=109)ACE基因插入／缺失(I／D)多态性之间的变化均无显著性差异。伴有尿微量蛋白增高EH患者收缩压和甘油三脂最高,靶器官损害多,D等位基因人数也最多。结论ACE基因多态性与EH发生关系不大,但D等位基因可能增加EH性肾损害的危险。