运动训练及依那普利对自发性高血压慢性肾功能衰竭大鼠模型肾功能的影响

目的:应用高血压肾功能衰竭大鼠模型,探讨运动训练与肾素血管紧张素转换酶抑制剂依那普利联合应用对肾功能的影响。方法:8周龄雄性自发性高血压大鼠24只,行右肾2/3切除,左肾全摘除,建立5/6肾切除自发性高血压慢性肾功能衰竭模型。于10周龄时,随机分为非运动组、中等强度运动训练组和运动训练加依那普利组。其中运动训练组所有动物进行跑台训练,速度20m/min,60min/d,5d/w。依那普利2mg/(kg·d)腹腔内持续给药。结果:4周运动训练明显抑制尿蛋白分泌,减小肾小球硬化指数。而运动训练加依那普利使血压明显下降和进一步减小肾小球硬化指数。结论:中等强度运动训练对慢性高血压肾功能衰竭模型有延缓肾衰进展、保护肾功能的作用。运动训练与依那普利联合应用能进一步增强这种肾脏保护作用。     

Protective effects of enalapril in streptozotocin-induced diabetic rat: studies of DNA damage, apoptosis and expression of CCN2 in the heart, kidney and liver

Diabetes mellitus is characterized by hyperglycemia, which induces oxidative stress and perturbs a number of pathways, leading to tissue injury. One of the pathological responses to tissue injury is the development of fibrosis and cell death. Enalapril is a non-thiol angiotensin-converting enzyme inhibitor that is commonly used in the treatment of diabetes-associated hypertension. The present study examines the possible beneficial effects of enalapril on the development of diabetes associated fibrosis and DNA damage in rats. Sprague-Dawley rats (250 ± 10 g) were used in the study. Enalapril (10 mg kg(-1) per oral) was administered for four consecutive weeks to the streptozotocin (STZ)-induced diabetic rats. After 4 weeks, all the animals were sacrificed and comet assay (normal and modified) was performed to detect the normal as well as oxidative DNA damage. Expression of profibrotic marker CCN2 and fibrosis was examined in the heart, kidney and liver of diabetic rats. Enalapril treatment significantly restored the malondialdehyde and glutathione content as well as the DNA damage in the heart, kidney and liver of diabetic rat. Significant decrease in the expression of CCN2 was observed in the heart, kidney and liver of diabetic rat receiving enalapril treatment as compared with the diabetic group. Further, the enalapril treatment led to significant decrease in the fibrosis and CCN2 expression in the diabetic group as compared with control. The results of the present study clearly demonstrate that enalapril ameliorates the DNA damage, cell death and expression of CCN2 in the heart, kidney and liver of the STZ-induced diabetic rat.     

厄贝沙坦与依那普利联用治疗肾性高血压的临床疗效分析

目的探讨治疗肾性高血压有效方法。方法选取我院2010年11月-2011年11月间入院治疗的96例肾性高血压患者为研究对象,按照治疗方法的不同分成厄贝沙坦组、依那普利组和联用组,每组32例患者。对患者治疗前后的相关资料进行了比较分析。结果厄贝沙坦组、依那普利组在收缩压和舒张压方面与联用组比较,P均〉0.05,差异无统计学意义;在尿蛋白方面厄贝沙坦组、依那普利组与联用组比较,P均〈0.05,差异具有统计学意义。结论厄贝沙坦与依那普利联用治疗肾性高血压的临床效果较好,是一种治疗肾性高血压的有效和安全的方法。     

依那普利对高血压患者心脏功能的影响

目的 探讨依那普利对高血压患者心脏功能的影响.方法 67例高血压患者中,36例服用硝苯地平缓释片加安慰剂作为对照组,31例服用硝苯地平缓释片加用依那普利作为依那普利组.治疗6个月后,在25 ℃环境中,利用多普勒超声检测两组空腹状态下心脏腔室大小、射血分数.结果 两组血压、心率明显下降,且依那普利组室间隔厚度、左室舒张末期内径、左室后壁厚度、射血分数较对照组改善更明显（P＜0.05）.结论 硝苯地平联合依那普利对高血压患者心脏功能有显著改善作用.     

高效液相色谱-质谱联用测定人血浆中的依那普利浓度

目的 :建立人血浆中依那普利的高效液相色谱 -质谱 (HPLC -MS)测定方法。方法 :样品血浆中加入内标阿普唑仑后 ,离心取上清液上固相萃取(SPE)小柱 ,以甲醇洗脱 ,采用HPLC -MS法 ,色谱柱为ODSC18,流动相为甲醇 -0 1%甲酸 (45∶55) ,流速为0 8ml/min。MS条件为 :ESI +源 ;毛细管电压 (Capillary) :3 81kV ;锥空电压 (Cone) :39 00V。选择离子峰检测。结果 :依那普利血浆药物浓度在2 5～400ng/ml范围内呈现良好的线性关系 ,r=0 9996 ,平均回收率为102 2 % ;日内RSD=4 0 % ,日间RSD=5 4%。结论 :该方法灵敏度高 ,无杂质干扰 ,测定结果准确 ,可用于依那普利片的人体药代动力学及相对生物利用度研究。     

氯沙坦联合依那普利治疗高血压逆转左室肥厚的临床观察

目的 观察氯沙坦联合依那普利治疗高血压逆转左室肥厚的疗效。方法 84例高血压左室肥厚(LVH)随机分为治疗组(45例)和对照组(39例)。治疗组给予氯沙坦联合依那普利治疗，对照组单用依那普利治疗，观察6个月。治疗前后分别测血压、室间隔厚度(LVST)、左室后壁厚度(PWT)、左室舒张束期内径(LVDd)、E、A、E/A计算左室重量指数(LVMI)。结果 两组血压均明显下降，组问比较治疗组LVST、PWT、LVMI、LVDd及E/A优于对照组。结论 氯沙坦联合依那普利在有效降压的同时，能更有效地逆转LVH，改善左室舒张功能。     

依那普利并氨氯地平对高血压大鼠血压及心血管结构的作用

①目的研究依那普利并氨氯地平对压力超负荷高血压大鼠血压、心肌纤维化与左室肥厚的影响.②方法将雄性Wistar大鼠随机分为5组,假手术组(S组)、手术组(O组)、依那普利组(E组)、氨氯地平组(A组)、联合用药组(C组).除假手术组只游离腹主动脉外,其余各组大鼠均行腹主动脉部分结扎术.S、O组分别将自来水5mL给大鼠灌胃,E、A组分别将20mg/kg依那普利和10mg/kg氨氯地平溶于5 mL自来水中给大鼠灌胃,C组将20mg/kg依那普利和10mg/kg氨氯地平给大鼠灌胃.术前及术后测大鼠血压,术后6周测定大鼠左心室质量指数(LVMI)、心肌胶原含量、心肌细胞凋亡指数(APOI)、心肌胶原容积分数(CVF)、心肌小动脉周围胶原面积与管腔面积比值(PVCA)、胸主动脉中膜/内径比值.③结果术后6周手术组大鼠心脏明显增大,左心室腔明显缩小,心肌显著肥厚.O组血压、LVMI、心肌胶原含量明显升高,与S组比较差异有显著性(F＝42.65～248.90,q＝16.27～38.32,P＜0.01);各用药组LVMI及心肌胶原含量低于手术组,差异有显著性(q＝5.44～69.56,P＜0.01);C组LVMI和心肌胶原含量低于A、E组,差异有显著性(q＝4.88～14.33,P＜0.01).各组APOI、CVF、PVCA和中膜/内径比值比较,差异有显著性(F＝12.52～172.06,P＜0.01);O组APOI、CVF、PVCA和中膜/内径比值高于S、E、A、C组,差异有显著性(q＝3.80～33.45,P＜0.05、0.01);C组APOI、CVF、PVCA及中膜/内径比值低于E、A组,差异有显著性(q＝3.25～14.42,P＜0.05、0.01).④结论依那普利与氨氯地平联用能有效逆转高血压引起的心血管肥厚,并具有较好的抗心肌细胞凋亡和心肌纤维化及降低血压的作用.     

COMPARISON OF THE PHARMACOKINETICS AND PHARMACODYNAMICS OF PERINDOPRIL, CILAZAPRIL AND ENALAPRIL

1. The pharmacokinetic and pharmacodynamic responses to enalapril, perindopril and cilazapril have been studied in essential hypertensives (2, 4 and 8 mg perindopril and 2.5 mg cilazapril, single dose and steady state) and normotensive volunteers (10 mg enalapril, single dose).
2. Plasma levels of the active diacid compounds reached similar peaks after single dose administration of the drugs. However, perindoprilat levels persisted for 5 days whereas cilazaprilat levels were not detectable beyond 12 h.
3. The higher levels of perindoprilat were associated with a greater inhibition of plasma angiotensin-converting enzyme (ACE) activity in both acute and steady state studies.
4. The potency of the active diacids in inhibiting plasma ACE activity was perindoprilat > cilazaprilat > enalaprilat.
5. There was a close relationship between plasma concentration, ACE inhibition and blood pressure decrease. Although both cilazapril and perindopril administration reduced blood pressure in hypertensive subjects, only perindopril exerted 24 h blood pressure control at the doses used.     

The Effects of Oral Atenolol or Enalapril Premedication on Blood Loss and Hypotensive Anesthesia in Orthognathic Surgery

Purpose

The aim of this study was to evaluate the effects of premedication with oral atenolol or enalapril, in combination with remifentanil under sevoflurane anesthesia, on intraoperative blood loss by achieving adequate deliberate hypotension (DH) during orthognathic surgery. Furthermore, we investigated the impact thereof on the amount of nitroglycerin (NTG) administered as an adjuvant agent.

Materials and Methods

Seventy-three patients undergoing orthognathic surgery were randomly allocated into one of three groups: an angiotensin converting enzyme inhibitor group (Group A, n=24) with enalapril 10 mg, a β blocker group (Group B, n=24) with atenolol 25 mg, or a control group (Group C, n=25) with placebo. All patients were premedicated orally 1 h before the induction of anesthesia. NTG was the only adjuvant agent used to achieve DH when mean arterial blood pressure (MAP) was not controlled, despite the administration of the maximum remifentanil dose (0.3 µg kg^-1min^-1) with sevoflurane.

Results

Seventy-two patients completed the study. Blood loss was significantly reduced in Group A, compared to Group C (adjusted p=0.045). Over the target range of MAP percentage during DH was significantly higher in Group C than in Groups A and B (adjusted p-values=0.007 and 0.006, respectively). The total amount of NTG administered was significantly less in Group A than Group C (adjusted p=0.015).

Conclusion

Premedication with enalapril (10 mg) combined with remifentanil under sevoflurane anesthesia attenuated blood loss and achieved satisfactory DH during orthognathic surgery. Furthermore, the amount of NTG was reduced during the surgery.     

Enalapril does not alter renal function in normotensive,normoalbuminuric, hyperfiltering Type 1 (insulin-dependent) diabetic children

Summary Using a prospective randomised double-blind crossover design, the effect of the angiotensin converting enzyme inhibitor enalapril compared to a placebo was studied in 18 normotensive, normoalbuminuric Type 1 (insulin-dependent) diabetic children. Each patient had a high normal or clearly elevated glomerular filtration rate (145 ml· min^–1· 1.73 m² or higher) in the 6 months prior to the study. Enalapril, 0.5 mg·kg^–1· day^–1, was given for 4 weeks followed by placebo for 4 weeks, or vice versa. At the end of each period, glomerular filtration rate, renal plasma flow, blood pressure, plasma renin activity, and converting enzyme activity were determined. Enalapril caused significant reduction (p=<0.001) in blood pressure and converting enzyme activity and a rise in plasma renin activity. A slight but not significant rise in glomerular filtration rate and renal plasma flow without change in filtration fraction was observed. These data suggest that the renin angiotensin system is not involved in the glomerular hyperfiltration of Type 1 diabetes, and can be interpreted as showing no evidence for the presence of intraglomerular hypertension in these patients.Recipient of the Schering Award of the Canadian Society of Clinical Investigation during the period of this research