Reduced progression of atherosclerosis in apolipoprotein E-deficient mice treated with lacidipine is associated with a decreased susceptibility of low-density lipoprotein to oxidation

A study has been carried out in the apolipoprotein (apo) E-deficient mouse to investigate the activity of lacidipine (a calcium antagonist with antioxidant properties) in inhibiting the development of atherosclerotic lesions; of particular interest were changes in the susceptibility of low-density lipoproteins (LDL) to oxidation. Mice receiving a Western-type diet to accelerate the development of atherosclerosis were treated orally with vehicle or lacidipine at 3 or 10 mg/kg/day for 8 weeks. Lacidipine treatment (at 3 or 10 mg/kg) had no effect on the plasma lipid profile. However, a significant (P < 0.01) dose-related reduction of 43 and 50% of the aortic lesion area in respect to vehicle-treated mice was observed. Moreover, the resistance of mouse plasma LDL to undergo lipid peroxidation was significantly (P < 0.01) increased in apo E-deficient mice treated with lacidipine. The native LDL-like particle, derived from apo E-deficient mice treated with lacidipine, contained significantly lower concentrations of malonyldialdehyde than the vehicle-treated control group (P < 0.01). After exposure to human umbilical vein endothelial cells, LDL-like particle vitamin E levels (expressed as area under the curve; AUC), were significantly higher (P < 0.01) in both the 3 and 10 mg/kg lacidipine-treated groups, in comparison with the vehicle-treated control animals. We conclude that lacidipine reduced the extent of the atherosclerotic area in hypercholesterolaemic apo E-deficient mice, and that this reduction may be associated with the capacity of the drug to decrease the susceptibility of LDL to oxidation.     

应用动态血压监测分析拉西地平的降压疗效

目的观察拉西地平的降压效应、耐受性、谷峰比值及不良反应.方法选择18例轻、中度原发性高血压患者,在服用安慰剂2周后,对随测舒张压在95～114-mmHg(1-mmHg＝0.133-kPa)的16名患者进行为期4周的药物治疗,给予拉西地平4-mg*d-1口服,治疗第2周末随测舒张压未能降至90-mmHg以下者,则剂量增至6-mg*d-1.于安慰剂导入期末和拉西地平治疗期末分别进行动态血压监测.结果服药后血压与用药前比较有显著下降.动态血压监测结果显示,治疗后总血压负荷、24-h、昼夜平均收缩压和舒张压均明显下降,收缩压和舒张压的谷峰比值均大于50%,心率在用药前后无明显变化.结论拉西地平治疗轻、中度原发性高血压有效、安全.     

MN9202对心肌细胞的收缩和舒张功能的影响

目的研究MN9202对心肌细胞收缩舒张功能的影响.方法采用IonOptix单细胞动缘检测系统(IonOptix Co.USA),测定心肌细胞收缩幅度和收缩/舒张速度等,这些指标均由计算机自动实时采集并记录.结果MN9202降低心肌收缩幅度(ph)、心肌细胞收缩幅度/单个心肌细胞的长度百分比(peak height/baseline×100%,ph/bl%)、最大收缩速率( dL/dt)和最大舒张速率(-dL/dt),ph在对照组、MN9202(3×10-6mol/L)组和拉西地平(lacidipine,3×10-6mol/L)组分别为(0.13±0.04)μm、(0.08±0.05)μm和(0.07±0.04)μm,ph/bl%分别为(8.6±2.8)%、(5.8±4.3)%和(5.6±3.3)%, dL/dt分别为(1.6±0.5)μm/s、(1.1±0.7)μm/s和(1.0±0.6)μm/s,-dL/dt分别为(1.2±0.4)μm/s、(0.8±0.3)μm/s和(0.7±0.3)μm/s.异丙肾上腺素(10-8mol/L,isoproterenol,Iso)增加ph、pl/bl%、 dL/dt和-dL/dt均有统计学意义,上述指标分别增加45%、47%、54%、78%.3×10-7mol/L的MN9202和拉西地平降低Iso引起ph、ph/bl%、 dL/dt和-dL/dt的升高,其中MN9202使 dL/dt和-dL/dt的降低较对照组有显著差异(P＜0.05),拉西地平使ph/bl%、 dL/dt和-dL/dt的降低较对照组有统计学意义.结论MN9202使心肌细胞收缩和舒张功能均降低;Iso所致心肌细胞收缩和舒张功能的增强,3×10-7mol/L MN9202和拉西地平有抑制Iso的作用.     

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。     

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。     

拉西地平对高血压病降压作用的临床研究

采用随机单盲对照试验法,观察了新型钙拮抗剂拉西地平与第二代钙拮抗剂尼群地平对原发性高血压病人的降压疗效。结果拉西地平降压总有效率达95.8％,副作用轻,有临床实用价值。     

拉西地平治疗重症高血压病的急性及慢性疗效观察

目的观察拉西地平对重症高血压病的急性及慢性降压疗效。方法采用动态血压及偶测血压的方法，测得３８例重症高血压病人平均血压在＞１８０／１２０ｍｍＨｇ，舌下含服拉西地平４ｍｇ，以后口服每天一次连续８周。结果急性降压效应，用药１２０ｍｉｎ时显效２２例，有效８例，无效８例。慢性降压效应，显效７０％，有效２５％，无效５％，平均谷／峰比值为０．７９。结论拉西地平适合于临床重症高血压的急性及慢性降压治疗。     

拉西地平对高血压病人胰岛素抵抗的影响

对20例高血压病(EH)患者拉西地平治疗前及治疗4周后,分别进行口服葡萄糖耐量试验(OGTT).并测定治疗前后血糖(SG)、血胰岛素(IS),与18例正常人(其年龄、体重指数相当)比较,结果:(1)降压作用:EH 组拉西地平治疗后血压较治疗前有显著降低(SBp:18.76±1.74kPa 比22.72±1.35kPa、DBp:11.76±1.23kPa 比14.31±1.14kPa)(P<0.05),总有效率达95%;(2)对 SG 影响:空腹血糖 EH 组较对照组无明显变化(P>0.05),OGTT 后 EH 组出现糖耐量异常达65%,治疗后血糖较治疗前略有下降,但无统计学差异;(3)对 IS 影响:EH 组血IS 空腹及 OGTT 后水平较对照组明显增高(P<0.05),IS/SG 比值空腹及 OGTT 后较对照组明显增高(P<0.05),IS 敏感性较对照组下降(0.11±0.03比0.19±0.03),EH 组拉西地平治疗后 IS 较治疗前下降。以0.5～1h 明显(0.5h:57.07±12.24mu/L 比77.26±14.49mu/L;1h:68.55±13.79mu/L 比90.09±15.25mu/L),(P<0.05),IS 敏感性较治疗前增加(0.14±0.06比0.11±0.03)。提示:EH 患者存在高胰岛素血症;拉西地平降压同时也降低了血 IS,增加了 IS 敏感性,使胰岛素抵抗得到了改善。     

DIABETIC RENAL MICROVASCULAR DISEASE: THE ROLE OF HYPERTENSION AND ACE INHIBITORS

1. It has been suggested that hypertension may be an important determinant of the rate of progression of diabetic microangiopathy.
2. Renal microvascular disease as assessed by urinary albumin excretion and glomerular ultra-structure was evaluated in a model in which streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR).
3. Diabetes was associated with increases in urinary albumin excretion, and hypertension resulted in a further increase in albuminuria.
4. Various antihypertensive regimens were administered to diabetic SHR, with the angiotensin-converting enzyme inhibitor perindopril and triple therapy (hydralazine, reserpine and hydrochlorothiazide) being more effective than the calcium antagonist (lacidipine) in retarding the increase in albuminuria in diabetic SHR.
5. Antihypertensive therapy appears to ameliorate the development of diabetic renal disease.