Department of Biopharmacy, Medical University of Lodz, Poland.
Arch Med Sci. 2012 Jul 4;8(3):549-54. doi: 10.5114/aoms.2012.29411.
β-Blockers play a significant role in therapeutic heart rate (HR) management and angina control. In patients who are unable to tolerate β-blockers ivabradine could be particularly useful. The aim of the study was to establish whether concomitant administration of simvastatin with ivabradine or metoprolol had any effect on rat HR and blood pressure (BP).
The experiments were performed in hyper- and normocholesterolemic outbred Wistar rats. Animals were divided into 2 groups: receiving during 4 weeks normal diet (normocholesterolemic rats) or diet with 5% cholesterol and 2.5% cholic acid (hypercholesterolemic rats). Then rats received placebo (0.1% methylcellulose), 2) metoprolol 30 mg/kg bw; 3) ivabradine 10 mg/kg bw; 4) simvastatin 10 mg/kg bw; 5) simvastatin 10 mg/kg bw + metoprolol 30 mg/kg bw; 6) simvastatin 10 mg/kg bw + ivabradine 10 mg/kg bw. Drugs were given during a 4-week period. HR and BP measure were provided by an Isotec pressure transducer connected to a direct current bridge amplifier. For the further lipid profile examination, 0.25 ml of blood samples were taken.
After administration of ivabradine with simvastatin to normocholesterolemic and hypercholesterolemic rats the mean HR was significantly reduced as compared to rats receiving simvastatin (312.0 ±30.2 min(-1) vs. 430.7 ±27.8 min(-1), p<0.05); (329.8 ±24.2 min(-1) vs. 420.5 ±9.2 min(-1), p<0.05) or ivabradine alone (312.0 ±30.2 min(-1) vs. 350.2 ±16.0 min(-1), p<0.05); (329.8 ±24.2 min(-1) vs. 363.0 ±21.7 min(-1), p<0.05).
Concomitant administration of simvastatin with ivabradine intensified slowing of HR, although it did not influence BP in normo-and hypercholesterolemic rats. Statin-induced intensification of HR deceleration after metoprolol administration was not observed.
β受体阻滞剂在治疗心率（HR）管理和心绞痛控制方面发挥着重要作用。对于不能耐受β受体阻滞剂的患者，伊伐布雷定可能特别有用。本研究旨在确定辛伐他汀与伊伐布雷定或美托洛尔联合使用对大鼠 HR 和血压（BP）是否有任何影响。
该实验在高胆固醇血症和正常胆固醇血症的近交 Wistar 大鼠中进行。动物分为两组：4 周内接受正常饮食（正常胆固醇血症大鼠）或含 5%胆固醇和 2.5%胆酸的饮食（高胆固醇血症大鼠）。然后，大鼠接受安慰剂（0.1%甲基纤维素）、2）美托洛尔 30mg/kg bw；3）伊伐布雷定 10mg/kg bw；4）辛伐他汀 10mg/kg bw；5）辛伐他汀 10mg/kg bw+美托洛尔 30mg/kg bw；6）辛伐他汀 10mg/kg bw+伊伐布雷定 10mg/kg bw。药物在 4 周内给予。心率和血压测量由与直流桥放大器相连的 Isotec 压力传感器提供。为了进一步检查血脂谱，采集 0.25ml 血样。
与接受辛伐他汀的正常胆固醇血症和高胆固醇血症大鼠相比，伊伐布雷定与辛伐他汀联合给药后大鼠的平均 HR 显著降低（312.0±30.2min(-1)vs.430.7±27.8min(-1)，p<0.05）；（329.8±24.2min(-1)vs.420.5±9.2min(-1)，p<0.05）或单独给予伊伐布雷定（312.0±30.2min(-1)vs.350.2±16.0min(-1)，p<0.05）；（329.8±24.2min(-1)vs.363.0±21.7min(-1)，p<0.05）。
辛伐他汀与伊伐布雷定联合给药可增强 HR 减慢，但对正常和高胆固醇血症大鼠的 BP 无影响。未观察到美托洛尔给药后他汀类药物引起的 HR 减速增强。
