The acute haemodynamic effects of quinapril,a new non-sulfhydryl angiotensin converting enzyme inhibitor,in patients with severe congestive cardiac failure

Summary This study investigates the acute haemodynamic effects of Quinapril (CI-906) a new non-sulphydryl angiotensin converting enzyme inhibitor in 15 patients with refractory congestive cardiac failure. There were 14 males and 1 female mean age 59.5 years.After administration of Quinapril there was a significant reduction in mean arterial pressure (MAP) from 93.1 to 79 mmHg, systemic vascular resistance (SVR) from 1887 to 1349 dyn s cm^–5 and PCW from 27.3 to 15.3 mmHg. This was accompanied by an increase in CO from 3.7 to 4.7 l/min, cardiac index (CI) from 1.97 to 2.5 l/min/m² and Stroke volume index from 21.1 to 28.7 ml/m². There was no significant change in heart rate (HR), right atrial pressure (RAP), or pulmonary vascular resistance.The peak effect on pulmonary capillary wedge pressure (PCW) and cardiac output (CO) occurred at 75–120 min after Quinapril administration. The maximum effect on mean arterial pressure (MAP) occurred slightly later at 120–150 min. SVR and CI exhibited 2 periods of peak effects, at 90 and 180 min. This time course is very similar to that observed in studies on the acute effects of Captopril.The significant improvement in haemodynamic measurements acutely, following administration of Quinapril 5 mg orally, suggests that this drug is worthy of further study in the management of patients with refractory congestive cardiac failure, in particular its long term effects.     

血管紧张肽转换酶抑制剂对高血压病人心脏和大动脉的影响

目的 :评价血管紧张肽转换酶 (ACE)抑制剂对原发性高血压病人心脏和大动脉结构和功能的影响。方法 :应用二维超声、超声心动图及自动脉搏波传导速度 (PWV)测定仪观察 16例采用ACE抑制剂培哚普利治疗 (4mg ,po ,qd ;4wk后若血压 >18.6 / 12 .0kPa ,加服吲哒帕胺 2 .5mg ,po ,qd)的原发性高血压病人心脏、大动脉结构和功能的改变 ,分别在治疗前和治疗 12wk后进行上述检测。结果 :收缩压、脉压、颈动脉 股动脉PWV、颈总动脉内膜 中层厚度和左室后壁厚度在 12wk培哚普利治疗后显著降低 [分别为 (2 0 .4±s 1.4 )kPavs (18.0± 1.2 )kPa ,(7.5± 1.1)kPavs (6 .9± 1.2 )kPa ,(10 .5± 1.3)m·s- 1vs (8.6± 1.0 )m·s- 1,(0 .71± 0 .14 )mmvs (0 .5 9± 0 .14 )mm ,(10 .5± 1.0 )mmvs (9.8± 1.0 )mm ,P <0 .0 1或P <0 .0 5 ];颈总动脉横断面顺应性、容积扩张性在治疗前后无显著性差异(P >0 .0 5 )。结论 :培哚普利对心血管系统的影响不仅仅是与血压降低有关 ,药物引起动脉平滑肌松驰 ,对全身和局部肾素 血管紧张肽系统的抑制能有效地改善高血压导致的心脏、血管结构和功能的改变。     

Effects of angiotensin converting enzyme inhibitor,perindopril, on autonomic reflexes

Summary The effect of the angiotensin converting enzyme inhibitor, perindopril, on autonomic function was assessed in a double blind, placebo controlled, crossover study in 10 normotensive males. Eight milligram of perindopril given orally lowered blood pressure without a change in heart rate. Perindopril enhanced the vagally mediated heart rate variation with deep breathing. There was no impairment of the responses to either bicycle exercise at 175 W for 5 min or isometric handgrip. The pressor response to cold was not changed and the response to the Valsalva manoeuvre was unaltered. These results suggest that the absence of tachycardia after perindopril may be in part related, as has been reported with other converting enzyme inhibitors, to enhanced cardiac parasympathetic tone. Vagomimetic action may be a property of converting enzyme inhibitors in general.     

血管紧张素转换酶抑制剂影响自发性高血压大鼠肾功能的机制

目的研究长期应用（4wk）卡托普利（30mg·kg-1）、依那普利（20mg·kg-1）和福辛普利（20mg·kg-1）3种血管紧张素转换酶抑制剂（ACEI）对自发性高血压大鼠（SHR）肾功能的影响以及与肾素-血管紧张素-醛固酮系统（RAA）、激肽释放酶-激肽系统（K-K）及前列腺素系统（PGS）的可能关系。方法测定血清及尿中的肌酐以计算肾小球滤过率、用放免法测定上述系统中有关活性物质在血浆、肾脏及尿中的浓度。结果3种ACEI均显著地降低SHR的血压。依那普利及福辛普利处理后SHR肌酐清除率分别为（370±112）及（380±110）ml·d-1，高于未处理SHR的滤过率（260±110，P＜0.05）。SHR用依那普利或福辛普利处理后血浆肾素活性及血管紧张素系Ⅰ（ATⅠ）浓度分别为（41±38）、（17±7）nmol·L-1·h-1及（12±8）、（14±10）nmol·L-1。肾脏肾素活性及ATⅠ浓度分别为（146±27）、（139±31）nmol·g-1蛋白·h-1及（85±25）、（95±23）nmol·g-1蛋白，均高于未处理组（P＜0.05）。SHR尿醛固酮排泄量在用卡托普利或依那普利处理后分别为（0.9±0.7）及（0.9±0.6）nmol·d-1，降至正常大鼠的水平，且低于未处理SHR（P＜0.05）。结论RAA在ACEI改善肾脏功能作用中起主要作用，而K-K及PGs不起重要作用。     

Haemodynamic effects of enalapril,a new converting enzyme inhibitor,in hypertensive patients

Summary The haemodynamic effects of enalapril (EN), a new, long-acting, nonsulphhydryl converting enzyme inhibitor, were evaluated by non-invasive methods in 10 adult patients with mild to moderate essential hypertension (EH). Patients were randomly assigned, double blind to 2 treatment groups (EN 20 mg o.d. or 10 mg b.d.) for 4 weeks, and were crossed over to the other dosage regimen after a 2-week washout period. Measurements included mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), limb blood flow (LBF), plasma aldosterone (ALD), plasma renin activity (PRA) and systolic time intervals (STI). Both regimens (b.d. and o.d.) significantly reduced MAP (15.3% and 16.3%, respectively), total peripheral resistance (20.3% and 21.8%, respectively), limb vascular resistance (24.1% and 24.9%) and ALD (33.5% and 36.9%) and increased CO (7.8% and 8.7%), LBF (10.9% and 11.6%) and PRA (10.4% and 9.5%). No significant change was observed in HR or STI. EN 20 mg o.d. or 10 mg b.d. reduced arterial pressure to a similar extent through a fall in total peripheral resistance. An increase in CO was also observed.     

Pharmacokinetics and haemodynamic effects of the angiotensin converting enzyme inhibitor cilazapril in hypertensive patients with normal and impaired renal function

1 The pharmacokinetic and pharmacodynamic properties of the angiotensin converting enzyme (ACE) inhibitor cilazapril were studied in 30 hypertensive patients with various degrees of renal function.
2 After a single oral dose, apparent cilazaprilat clearance was dependent on renal function being 16.0±3.0, 11.1 ± 3.0, 8.7 ± 3.7 and 6.7 ± 2.1 l h^-1 (means ± s.d.) in patients with creatinine clearances (CL_cr) of > 100, 41-100, 21-40, and 8-20 ml min^-1, respectively.
3 During 11 weeks of treatment with cilazapril, doses were adjusted to the CL_cr and varied from 0.5 to 5.0 mg once daily. At 24 h after drug administration a clear antihypertensive response was seen only in the low clearance groups (CL_cr < 40ml min^-1). In contrast, and despite higher once daily dosages, the decline of mean arterial pressure was small and cilazaprilat concentrations after 24 h were lower in the high clearance groups.
4 This study demonstrates that chronic once daily treatment with cilazapril is effective in patients with impaired renal function at dosages adjusted to creatinine clearance. No accumulation was seen. Since cilazaprilat clearance was high in the high creatinine clearance groups, a clear antihypertensive response in these groups was only seen at 3 h after drug administration.     

培哚普利对慢性缺氧高二氧化碳大鼠肺血管重建的影响

目的 探讨培哚普利对常压慢性缺氧高二氧化碳性肺动脉高压及肺血管重建的影响。方法 47只SD大鼠随机分为：对照组（A）、缺氧高二氧化碳处理4wk组（B1）、培哚普利治疗4wk组（B2）、缺氧高二氧化碳处理8wk组（C1）、培哚普利治疗8wk组（C2)。采用常压低氧高二氧化碳肺动脉高压大鼠模型,观察肺动脉平均压（mPAP),血浆血管紧张素Ⅱ（AngⅡ） 及肺小血管平滑肌外膜、内膜超微结构的变化,以及培哚普利对以上变化的影响。结果 缺氧高二氧化碳使mPAP,AngⅡ上升,超微结构发生变化,培哚普利治疗4wk组mPAP,AngⅡ下降,平滑肌超微结构病变减轻。培哚普利治疗8wk组,平滑肌超微结构病变与对照组相似。结论 提示缺氧高二氧化碳使肺血管重建,且与AngⅡ有关;培哚普利能在一定程度上能减轻肺血管重建。     

新型血管紧张素转换酶抑制剂的临床应用

本文综述培哚普利、雷米普利、贝那普利、喹那普利、福辛普利等新型血管紧张素转换酶抑制剂的药物动力学特点，以及在高血压、充血性心力衰竭的临床近况、与卡托普利比较，它们大多半衰期长、作用持久、服用方便（每日１次），不良反应相似但发生率略低。预期在今后心血管疾病治疗中将发挥重要作用。     

血管紧张肽转换酶抑制药在冠心病治疗中的应用

血管紧张肽转换酶抑制药可通过改善心肌供氧耗氧平衡、改善血管内皮功能、抑制交感神经兴奋性、抑制血管平滑肌迁移和增殖、抑制血小板聚集和促进纤维蛋白溶解、抑制低密度脂蛋白氧化修饰、抑制心肌肥厚、延迟心脏重构等机制在动脉粥样硬化和冠心病的治疗中发挥重要作用     

血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂在慢性心力衰竭治疗中的应用

心力衰竭是多种心脏病的最终死亡原因,阻断肾素-血管紧张素-醛固酮系统(renin angiotensin aldosterone system,RAAS)是减慢心力衰竭病变进展的主要策略。血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitors,ACEI)和血管紧张素受体拮抗剂(angiotensin receptor blockers,ARB)是目前最常用的阻断RAAS的药物。本文对慢性心力衰竭评估,以及ACEI和ARB在慢性心力衰竭治疗中的应用进行综述。     

骨化三醇联合缬沙坦对糖尿病肾病肾素、血管紧张素及血管紧张素转换酶表达的影响

目的 探讨骨化三醇联合缬沙坦对糖尿病肾病（DN）患者肾素、血管紧张素Ⅱ（AngⅡ）、血管紧张素转换酶（ACE）表达的影响。方法 按随机数字表法将2014年1月-2017年7月北京怀柔医院接诊的60例DN患者分为两组,对照组30例接受缬沙坦治疗,观察组30例接受骨化三醇联合缬沙坦治疗。连续用药6个月后,比较两组肾素、AngⅡ、血肌酐（Scr）、ACE、ACE2、糖代谢指标[糖化血红蛋白（HbA1c）、空腹血糖（FPG）]、蛋白尿相关指标[24 h尿蛋白、尿蛋白排泄率（UAER）、尿微量白蛋白（mAlb）、尿α1-微球蛋白（α1-MG）]水平。结果 治疗后观察组Scr、AngⅡ、肾素水平分别为（72.15±7.19）μmol/L、（81.24±9.12）ng/L、（104.32±10.37）ng/L,对照组Scr、AngⅡ、肾素水平分别为（83.64±7.43）μmol/L、（86.36±10.09）ng/L、（117.69±8.75）ng/L,差异具有统计学意义（P<0.05）;观察组24 h尿蛋白、UAER、mAlb、α1-MG水平低于对照组,差异具有统计学意义（P<0.05）;观察组和对照组ACE水平分别为（7.79±2.31）pg/mL、（14.82±4.56）pg/mL,差异具有统计学意义（P<0.05）;两组ACE2、Hb A1c、FPG水平比较,差异无统计学意义。结论 对DN患者采用骨化三醇联合缬沙坦治疗效果显著,能有效抑制肾脏ACE表达,降低AngⅡ、肾素水平,改善蛋白尿症状,提高肾功能,对延缓DN病情发展起到重要的作用。     

The effect of the converting enzyme inhibitor HOE 498 on the renin angiotensin system of normal volunteers

Summary The converting enzyme inhibitor HOE 498 was evaluated in 12 normotensive male volunteers aged 21 to 26. The efficacy of single 5, 10 or 20 mg oral doses in blocking the pressor response to exogenous angiotensin I was tested in 3 of the subjects. All 3 doses of HOE 498 reduced the pressor response to exogenous angiotensin I to below 50% of control within 1,5 h following administration of the drug. Plasma renin and converting enzyme activity, blood angiotensin I, as well as plasma angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of a single dose of 2.5, 5, 10 or 20 mg of HOE 498 to groups of 5 volunteers each. As expected, blood angiotensin I levels and plasma renin activity rose while plasma converting enzyme activity, plasma angiotensin II and aldosterone concentration fell after administration of the drug. While the dose of 2.5 mg did not reduce plasma converting enzyme activity below 20% of control, the higher doses all resulted in plasma converting enzyme inhibition exceeding 90%. No side-effects were observed. It is concluded that in normal volunteers HOE 498 is an effective potent and long-acting converting enzyme inhibitor. Based on these preliminary findings it is expected that 5 mg HOE 948 will turn out to be adequate for therapeutic use.     

ACE抑制剂卡托普利对实验性围手术期心肌缺血的影响

目的:图手术期心肌缺血主要是因为应激引起冠状动脉内皮功能障碍所致,所以观察卡托普利对其影响。方法:杂种犬20只均分为4组:Ⅰ组(对照组),Ⅱ组(心肌梗塞模型组),Ⅲ组(心梗 胃大部切除术)和Ⅳ组(心梗 卡托普利 胃大部切除术)。心梗2周后行胃大部分切除术,测定Ⅲ、Ⅳ两组的基础状态、术前和术后的血流动力学指标、血浆内皮素(ET)及一氧化氮(NO)。用组织原位杂交方法观察4组非梗塞区冠脉内皮-氧化氮合酶(NOS)mRNA表达水平。结果:在Ⅲ组,手术使LV dP/dt_(max)、心脏指数(CI)及NO下降,引起LVEDP、PCWP、总外周阻力(TPR)、左室舒张压力下降时间常数(T值)和ET升高。在Ⅳ组,用卡托普利后40min,TPR下降,T值升高;手术使血流动力学指标回降,不影响其它指标。组织原位杂交示,NOS mRNA在Ⅰ组高度表达,Ⅱ组和Ⅳ组次之,Ⅲ组最低。结论:卡托普利能预防胃大部切除术引起的左室舒缩障碍和冠脉内皮功能障碍。     

Effect on blood pressure and the renin-angiotensin system of repeated doses of the converting enzyme inhibitor CGS 14824A

Summary A new, orally active angiotensin converting enzyme (ACE) inhibitor, CGS 14824A, was evaluated in 12 healthy male volunteers. Two groups each of 6 volunteers were given 5 or 10 mg once daily p.o. for 8 days. Four hours after the first and the last morning doses, plasma angiotensin II, aldosterone and plasma converting enzyme activity had fallen, while blood angiotensin I and plasma renin activity had risen. Throughout the study, more than 90% inhibition of ACE was found immediately before giving either the 5 or 10 mg dose and 50% blockade was still present 72 h following the last dose. Based on the determination of ACE, there was no evidence of drug accumulation. No significant change in blood pressure or heart rate was observed during the course of the study. CGS 14824A was an effective, orally active, long-lasting and well tolerated converting enzyme inhibitor.     

亲和色谱法从猪骨胶原蛋白酶解物中分离纯化血管紧张素转换酶抑制剂

目的从猪骨胶原蛋白酶解物中分离出高纯度的血管紧张素转换酶抑制剂。方法将胶原蛋白酶解物用双蒸水溶解 ,先上SephadexG 2 5柱 ,用含有 10mmol/L吡啶的 0 .6mol/L醋酸溶液洗脱 ,收集对血管紧张素转换酶有抑制作用的峰值部分冻干 ;再上血管紧张素转换酶抑制剂亲和柱洗脱 ,测定各收集管洗脱液的比抑制活力 ,收集峰值部分冻干。结果亲和色谱柱洗脱液峰值管比抑制活力达 14 5 0u/mg,为粗提液的 90 6倍 ,活力回收率为 12 .1%。结论利用亲和色谱法 ,能够从猪骨胶原蛋白酶解物中分离出高纯度的血管紧张素转换酶抑制剂。     

Angiotensin converting enzyme 2 in the kidney

1. Angiotensin converting enzyme 2 (ACE2) is an important homeostatic component of the renin angiotensin system (RAS). ACE2 both degrades the vasoconstrictor, angiotensin II and generates the potent vasodilator peptide, angiotensin 1-7. These actions counterbalance those of ACE. 2. ACE2 is highly expressed in the healthy kidney, particularly in the proximal tubules, where it colocalizes with ACE and angiotensin receptors. 3. Kidney disease and subtotal nephrectomy is associated with a reduction in renal ACE2 expression, possibly facilitating the damaging effects of angiotensin II in the failing kidney. Acquired or genetic ACE2 deficiency also appears to exacerbate renal damage and albuminuria in experimental models, supporting this hypothesis. 4. ACE2 also has an important role in blood pressure control. Many models of hypertension are associated with reduced ACE2 expression. Although ACE2 KO animals are normotensive, in states associated with activation of the RAS, ACE2 overexpression improves blood pressure control and reduces angiotensin responsiveness.     

Laboratory monitoring of potassium and creatinine in ambulatory patients receiving angiotensin converting enzyme inhibitors and angiotensin receptor blockers

PURPOSE: Serum potassium and creatinine monitoring is recommended for patients prescribed angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). Much has been written about hyperkalemia associated with these drugs; little is known about laboratory monitoring patterns. The purpose of this retrospective cohort study was to assess creatinine and potassium monitoring and characteristics associated with monitoring among patients dispensed ACEi or ARB. METHODS: This study was conducted in 10 United States health maintenance organizations. Study patients (n = 52 906) were aged 18 or older with dispensings of ACEi or ARB for at least 1 year. Serum potassium and creatinine monitoring were assessed from administrative data and medical records. RESULTS: More than two-thirds (68.4%) of patients received laboratory monitoring. Likelihood of monitoring increased with age (adjusted odds ratio [OR] 2.10; 95% confidence interval [95%CI] 1.93, 2.28 [individuals >or= 80 compared to <50 years]), >9 outpatient visits (OR 1.46; 95%CI 1.39, 1.54), hospitalization (OR 1.15; 95%CI 1.06, 1.25), concomitant medications (potassium [OR 2.01; 95%CI 1.84, 2.20], diuretics [OR 1.54; 95%CI 1.47, 1.61], digoxin [OR 1.15; 95%CI 1.01, 1.30]), and comorbidities (diabetes [OR 1.68; 95%CI 1.61, 1.75], heart failure [OR 1.73; 95%CI 1.57, 1.90], chronic kidney disease [OR 2.95; 95%CI 2.48. 3.51]). CONCLUSIONS: Nearly one-third of patients dispensed ACEi or ARB did not undergo laboratory monitoring at least yearly. Though patients at increased risk of hyperkalemia were more likely to be monitored, many remained unmonitored.     

缬沙坦及苯那普利对慢性肾衰竭大鼠心肌病变的治疗作用

目的观察缬沙坦、苯那普利及缬沙坦和苯那普利联用对慢性肾衰竭大鼠心肌病变的改善作用,探讨其作用机制。方法SD♂大鼠40只,通过5/6肾切除法制备慢性肾衰竭模型,术后2wk随机分为模型组、缬沙坦组、苯那普利组及缬沙坦与苯那普利联合治疗组,并设假手术组作为对照。术后第10周末测定各组大鼠血压及肾功能(Scr、BUN)后处死大鼠,取出心脏进行病理组织学观察;并采用原位杂交方法检测心肌内皮素-1(ET-1)mRNA及一氧化氮合酶3(eNOS-3)mRNA的转录水平。结果模型组术后第10周收缩压、心脏重量、心脏重量指数、左室重量及左室重量指数均明显增加,缬沙坦、苯那普利及联合治疗组能明显降低5/6肾切除大鼠收缩压、心脏重量、心脏重量指数、左室重量及左室重量指数(P<0.01);缬沙坦组、苯那普利组及联合治疗组心肌ET-1mRNA、eNOS-3 mRNA转录水平均较模型组减弱。结论缬沙坦、苯那普利及缬沙坦与苯那普利联合治疗能防治慢性肾衰竭大鼠的左室肥厚,其机制可能是通过下调心肌ET-1 mRNA、eNOS-3 mRNA转录来实现的。     

Effect of L-thyroxine on serum angiotensin converting enzyme activity in sheep

The effect of L-thyroxine on serum angiotensin converting enzyme activity using a sheep model was examined. Following two weeks of L-thyroxine treatment, the activity of serum angiotensin converting enzyme was increased from 6.92 U/ml to 8.65 U/ml (s.e.m. = 0.40, n = 13, P less than 0.01). Discontinuation of L-thyroxine treatment resulted in lowering the activity of serum angiotensin converting enzyme within three weeks to values close to those observed during the control period. It was concluded that L-thyroxine modulates serum angiotensin converting enzyme activity. The sheep is an appropriate animal model for the study of the factors that control serum angiotensin converting enzyme activity.