Zhuang Han-ping, Li Jing, Liu Li-hua
Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, China.
Hunan Yi Ke Da Xue Xue Bao. 2003 Feb 28;28(1):37-40.
To explore the interactive effect of low-dosage aspirin (ASA) combined with perindopril (PER), on prostacyclin (PGI2), thromboxone A2 (TXA2), and norepinephrine (NE) in the blood of arteriosclerosis rabbit models and the cardiac function.
Sixty adult New Zealand rabbits were randomly distributed into 5 groups with 12 rabbits in each group. One group was fed with standard fodder; the others were fed with high lipoid-diet (1% cholesterol content). Before and after 8 weeks' administration consecutively, LVEDP, LVSP, HR, +/- dp/dtmax, plasma PGI2 and TXA2, serum NE, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-ch), high-density lipoprotein cholesterol (HDL-ch) and triglycerides (TG) were evaluated.
TG, TC, LDL-ch and pathological results confirmed arteriosclerosis rabbit models successfully. ASA combined with PER led to a significant increase in PGI2/TXA2 (P < 0.01) together with a significant decrease in the NE levels (P < 0.01) in the rabbits' blood, and then improved the cardiac output, i.e. increased LVSP (P < 0.01), and decreased the heart rate (P < 0.01) and LVEDP (P < 0.01) to a greater extent in the arteriosclerosis rabbit models.
The ratio of PGI2 to TXA2 increased, and the NE levels decreased significantly; meanwhile, the heart rate decreased and the cardiac function improved during the administration of aspirin combined with perindopril in arteriosclerosis rabbit models. The results suggest that there is a synergism-action between low-dosage aspirin and ACE inhibitors due to increased PGI2/TXA2 and decreased NE levels.
探讨小剂量阿司匹林(ASA)联合培哚普利(PER)对动脉粥样硬化兔模型血液中前列环素(PGI2)、血栓素A2(TXA2)和去甲肾上腺素(NE)的相互作用以及对心功能的影响。
将60只成年新西兰兔随机分为5组,每组12只。一组给予标准饲料;其他组给予高脂饲料(胆固醇含量1%)。连续给药8周前后,评估左室舒张末压(LVEDP)、左室收缩压(LVSP)、心率(HR)、±dp/dtmax、血浆PGI2和TXA2、血清NE、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-ch)、高密度脂蛋白胆固醇(HDL-ch)和甘油三酯(TG)。
TG、TC、LDL-ch及病理结果证实成功建立动脉粥样硬化兔模型。ASA联合PER可使兔血液中PGI2/TXA2显著升高(P<0.01),同时NE水平显著降低(P<0.01),进而改善心输出量,即动脉粥样硬化兔模型中LVSP升高(P<0.01),心率(P<0.01)和LVEDP降低(P<0.01)幅度更大。
在动脉粥样硬化兔模型中,阿司匹林联合培哚普利给药期间,PGI2与TXA2的比值升高,NE水平显著降低;同时心率降低,心功能改善。结果表明,由于PGI2/TXA2升高和NE水平降低,小剂量阿司匹林与ACE抑制剂之间存在协同作用。