吡那地尔对高血压心脏结构和功能重构的影响

在等降压剂量下吡那地尔和赖诺普利可使４月龄自发性高血压大鼠的血压下降６．０￣８．０ｋＰａ，并接近同种属正常血压大刀瓣血压水平。     

ACE基因多态性及循环中酶活性与EHT的关系及赖诺普利对其疗效的观察

对１１０例原发性高血压（ＥＨＴ）患者和１６３例正常对照者取血测定其血管紧张素转换酶（ＡＣＥ）基因Ｉ与 Ｄ多态性及循环中酶活性。高血压组Ｄ等位基因频率高于对照组,分别为 ０．５１８　２和０．４３２ ５（Ｐ＜０．０５）。两组中ＡＣＥ活性均存在ＤＤ＞ＩＤ＞Ⅱ。高血压组及对照组ＩＤ型ＡＣＥ活性分别为３１４．１±６７．９４和２５８．３５±６４．１１（Ｐ＜０．０１）,Ⅱ型分别为２５９．６８±６９．６８和２２０．８８±６２．８５（Ｐ＜０．０５）。高血压组应用赖诺普利后各基因型患者血压均有明显下降,降压幅度ＤＤ＞ＩＤ＞Ⅱ。结果显示ＡＣＥ基因多态性与原发性高血压有密切关系,ＤＤ型有高易患性。ＡＣＥ活性受基因型控制,ＤＤ型活性最高。应用赖诺普利后各基因型血压均有下降,降压幅度 ＤＤ＞ ＩＤ＞ Ⅱ。 ＤＤ型可作为ＡＣＥ抑制剂应用的最佳指征。     

Evaluation of amlodipine, lisinopril, and a combination in the treatment of essential hypertension

Angiotensin converting enzyme (ACE) inhibitors and dihydropyridine calcium antagonists are well established and widely used as monotherapy in patients with mild to moderate essential hypertension. Earlier studies combining short acting drugs from these classes require multiple dosing and were associated with poor compliance. Availability of longer acting compounds allows once daily administration to avoid the inconvenience of a multiple daily dose. It was decided to perform a randomised double blind, crossover study with the long acting calcium channel blocker amlodipine and the long acting ACE inhibitor lisinopril, given either alone or in combination in essential hypertension. Twenty four patients with diastolic blood pressure (DBP) between 95 and 104 mm Hg received amlodipine 2.5 mg and 5 mg, lisinopril 5 mg and 10 mg, and their combination as per a prior randomisation schedule. Supine and standing blood pressure and heart rate were recorded at weekly intervals. Higher doses of both the drugs individually or in combination were used if the target supine DBP below 90 mm Hg was not achieved. There was a significant additional blood pressure lowering effect with the combination when compared either with amlodipine or lisinopril alone. Five mg amlodipine and 10 mg lisinopril monotherapy achieved the target blood pressure in 71% and 72% patients respectively. The combination of 2.5 mg amlodipine with 5 mg lisinopril produced a much more significant lowering of blood pressure in a higher percentage of patients than that with an individual low dose.     

比索洛尔、拉西地平和赖诺普利对高血压病患者24小时血压的影响

目的比较比索洛尔、拉西地平和赖诺普利对２９例高血压病患者的降压疗效。方法采用随机、单盲和交叉的方法，运用２４小时动态血压监测。结果三药均能显著降低血压，彼此间降低偶测血压的幅度无显著差异。比索洛尔和拉西地平降低２４小时平均和白天平均血压的幅度大于赖诺普利。三药均能有效控制清晨血压高峰期的血压，它们的降压谷／峰比值都超过６５％。结论比索洛尔、拉西地平和赖诺普利均可每日服用１次，前二药控制２４小时血压及清晨醒后的高峰期血压较后者为佳。     

盐酸埃他卡林的降压作用及对高血压血管重构的影响

目的 在自发性高血压大鼠(spontaneously hypertensive rat,SHR)上，评价盐酸埃他卡林(Iptakalim hydroehlo-ride,Ipt)对高血压血管重构的实验治疗学作用。方法 21只12周龄SHR随机分为3组：Ipt 3mg/kg治疗组，赖诺普利(lisinopril,Lis)12mg/kg治疗组和空白对照组。另设同月龄正常血压Wistar大鼠为正常对照组。大鼠ig Ipt、Lis或蒸馏水10ml/kg，每日1次，连续4周，观察药物对高血压血管重构的影响。结果 实验期4周内，SHR对照组血压和心率持续性进行性增高。其主动脉中层壁显著增厚，中层壁厚与内径的比值(M/L)也显著增大；肠系膜动脉的中层壁显著增厚，内径显著变小，二者的比值显著增大，表明高血压时动脉的结构发生了重构。Ipt能有效控制SHR的血压，降压效果确切，且可抑制SHR心率加快的趋势 ；Ipt治疗可阻止肠系膜动脉和主动脉的结构重构。相同实验条件下，Lis也均能有效控制SHR的血压，降压效果确切，对心率无明显影响；Lis治疗也可阻止肠系膜动脉和主动脉的结构重构。结论 Ipt能有效地控制SHR的血压，可以阻止高血压血管结构重构。     

赖诺普利对百草枯中毒肺纤维化的作用

目的探讨赖诺普利（ACE-1）对百草枯中毒肺纤维化作用及其机制。方法：清洁级成年Wistar大鼠（体重150～300g）50只。被分为5组：组1予生理盐水，组2予赖诺普利（1mg／kg：PO），组3予单剂量百草枯（20mg／kg），组4（治疗组）：予百草枯后再给予赖诺普利，组5（预治疗组）：予赖诺普利后再给予百草枯。21天后，测量大鼠肺组织羟脯胺酸含量（hydroxyproline，Hyp）和过氧化脂质（LPO），一部分肺组织作病理组织学检查。结果百草枯显著的增加肺组织羟脯胺酸含量而赖诺普利显著降低大鼠肺组织中羟脯胺酸含量，组织学检查亦显示赖诺普利能有效地保护百草枯诱导的肺纤维化。脂质过氧化水平与对照组相比并无显著改变。结论赖诺普利可能是通过抑制血管紧张素Ⅱ的产生发挥其抗纤维化作用。     

Can angiotensin converting enzyme inhibitors prevent postoperative adhesions?

BACKGROUND: Peritoneal adhesions are pathological fibrotic bands developing after mesothelial damage. Transforming growth factor beta-1 (TGF-beta1) has mitogenic activities for macrophages and fibroblasts. Over-expression of TGF-beta1 has been implicated in the pathogenesis of several fibrotic disorders. Angiotensin II increases the expression of the TGF-beta1 in fibroblasts. The aim of the study was to investigate the effect of angiotensin converting enzyme inhibitor (ACE) on intraperitoneal adhesions. MATERIALS AND METHODS: Thirty male Wistar albino rats were divided into two groups. In the first procedure, laparotomy was performed through a 3-cm midline incision. Ileum was divided above 10 cm from ileocecal valve and a single-layer ileoileal anastomosis was performed. Although no treatment was given to rats in group 1, lisinopril (an ACE inhibitor) was given to rats in group 2 for postoperative 7 days in drinking water. Estimated amount of supplied lisinopril was 6.5 mg/kg/day. On postoperative 8th day, relaparotomy was performed and adhesions were evaluated. At the same time, blood samples were taken for TGF-beta1 measurements. RESULTS: Adhesion severity was significantly less in the ACE inhibitor group (P < 0.001). While mean TGF-beta1 level was 860.3 +/- 108.1 pg/dl (mean +/- SD) in control group, it was 335.8 +/- 52.4 pg/dl in ACE inhibitor group (P < 0.001). There was a significant correlation between serum TGF-beta1 levels and grade of adhesions (r = 0.948). CONCLUSION: It was concluded that ACE inhibitors might be useful for preventing peritoneal adhesions.     

Early rather than delayed administration of lisinopril protects the heart after myocardial infarction in rats

Background:ACE inhibitors have shown beneficial results in several studies after myocardial infarction (MI). However, this studies have shown conflicting results about the ideal starting time of the ACE inhibitors administration after MI and the importance of infarct size. Objectives: This study was designed to assess the long-term effects of lisinopril on mortality, cardiac function, and ventricular fibrosis after MI, in rats. Methods: Lisinopril (20 mg/kg/day) was given on day 1 or 21 days after coronary occlusion in small or large infarctions. Results: The mortality rate was reduced by 39% in early treatment and 30% in delayed treatment in comparison to the untreated rats. Early treatment reduced cardiac dysfunction in small MIs; however, delayed treatment did not. No statistical difference was observed among the groups for large MIs. No statistical difference was observed among the groups with large or small MIs on myocardial hydroxyproline concentration. Conclusions: Both early and delayed treatments with lisinopril increased survival. Treatment exerts no marked effects on fibrosis; early treatment has exerted beneficial influences on cardiac function whereas delayed treatment had no consistent effects. The protective effect of lisinopril is detectable only in small (< 40% of LV) MIs. Received: 6 May 1999, Returned for 1. revision: 28 May 1999, 1. Revision received: 20 July 1999, Returned for 2. revision: 26 August 1999, 2. Revision received: 28 September 1999, Accepted: 29 September 1999     

赖诺普利/氢氯噻嗪复方片在中国健康志愿者中的药代动力学研究(英文)

本研究描述了赖诺普利/氢氯噻嗪复方片在中国健康人体内的药代动力学特征。9名受试对象分别服用高、中、低3种剂量的复方片剂,结果表明,两种药物的AUC和Cmax都随着剂量的增加显著增加,但3种剂量间AUC/Dose、Cmax/Dose和tmax无明显差别。赖诺普利和氢氯噻嗪在涉及剂量范围内呈线性代谢特征。8名健康受试者在多次服用赖诺普利/氢氯噻嗪复方片后,与第1次服药比较,达稳态后的赖诺普利的AUC、Cmax和Cmin有所增加,其中AUC和Cmax显著增加;氢氯噻嗪的AUC、Cmax、Cmin和tmax有所增加,其中AUC和Cmin显著增加。达稳态后,赖诺普利的波动指数(FI)为2.29,浓度较为平稳,而氢氯噻嗪的波动指数FI为4.09,浓度相对波动较大。     

拉西地平与赖诺普利对高血压患者昼夜血压的影响

目的：比较拉西地平和赖诺普利对高血压患者的疗效。方法：６０例高血压病Ⅰ期或Ⅱ期患者按服药情况分拉西地平组、赖诺普利组、治疗８ｗｋ进行２４ｈ动态血压监测。结果：两药均能显著降低，降低偶测ＢＰ的幅度无显著差异，拉西地平降低２４ｈ平均压和白天平均压的幅度大于赖诺普利。结论：对轻中度高血压病拉西地平与赖诺普利是一种安全的药物，ｑｄ给药能维持２４ｈ降压效应。