Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
J Hypertens. 2012 Sep;30(9):1782-90. doi: 10.1097/HJH.0b013e3283562e35.
The effect of brief, prehypertensive therapy by angiotensin-converting enzyme inhibition (ACEi) with perindopril on the structure and function of large arteries was studied in rats.
Spontaneously hypertensive rats (SHR) received perindopril (3 mg/kg per day) between the ages of either 6 and 10 weeks (early) or 20 and 24 weeks (late) and compared with nonmedicated SHR and normotensive (Wistar-Kyoto) controls (n = 6 per group). Haemodynamic parameters and segmental aortic stiffness assessed by pulse wave velocity (PWV) were measured under urethane anaesthesia [1.3 g/kg, intraperitonealy (i.p.)] at 25 weeks. Aortic elastin and collagen content were determined by histomorphometry and calcium content by atomic absorption spectrophotometry.
Rats receiving brief, early perindopril therapy had lower tail-cuff SBP than nonmedicated SHR (121 ± 1 mmHg, 179 ± 5 mmHg, respectively, P < 0.05), reflected in lower thoracic and abdominal aortic pulse pressures. Aortic pulse pressure amplification was lower with early perindopril treatment (early treated 10 ± 5%, nonmedicated 20 ± 10%, P < 0.05). No blood pressure (BP) differences were observed between late treated and nonmedicated SHR. Isobaric thoracic PWV was lower when treated early but not later in life. Treatment did not alter abdominal PWV. Early treatment was associated with reduction in total aortic calcification (48%, P < 0.001) and reduction in medial cross-sectional area (40%, P < 0.05) of abdominal aorta compared with nonmedicated rats. Treatment increased the wall thickness/diameter ratio, but only early treated rats had a 46% higher elastin/collagen ratio compared with SHR controls.
Early but not late brief ACEi decreased arterial pressure and isobaric wall stiffness in SHR. This was associated with marked alteration of wall structure and the effects persisted after cessation of early treatment. The structural mechanisms responsible for this change varied segmentally along the aortic trunk.
研究血管紧张素转换酶抑制剂（ACEi）培哚普利对血压正常前期大鼠的大动脉结构和功能的短期降压治疗作用。
6-10 周龄（早期）或 20-24 周龄（晚期）的自发性高血压大鼠（SHR）接受培哚普利（3mg/kg/天）治疗，并与未治疗的 SHR 和正常血压（Wistar-Kyoto）对照（每组 6 只）进行比较。在 25 周时，通过脉搏波速度（PWV）评估在 1.3g/kg 乌拉坦麻醉下（腹腔内）的血流动力学参数和节段性主动脉僵硬度。通过组织形态计量法测定主动脉弹力蛋白和胶原含量，通过原子吸收分光光度法测定钙含量。
接受短期早期培哚普利治疗的大鼠尾套收缩压低于未治疗的 SHR（121±1mmHg，179±5mmHg，P<0.05），这反映在胸主动脉和腹主动脉脉搏压降低。早期培哚普利治疗时，主动脉脉搏压放大率较低（早期治疗 10±5%，未治疗 20±10%，P<0.05）。晚期治疗的 SHR 与未治疗的 SHR 之间的血压差异无统计学意义。早期治疗时胸主动脉等压 PWV 降低，但晚期治疗时则没有。治疗未改变腹主动脉 PWV。与未治疗的大鼠相比，早期治疗与总主动脉钙化减少（48%，P<0.001）和腹主动脉中层截面积减少（40%，P<0.05）相关。治疗增加了壁厚度/直径比，但只有早期治疗的大鼠与 SHR 对照组相比，弹力蛋白/胶原比增加了 46%。
短期早期 ACEi 可降低 SHR 的动脉压和等压壁僵硬度。这与壁结构的明显改变有关，并且在早期治疗停止后仍持续存在。这种变化的结构机制在主动脉干的各个节段有所不同。
