Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.
Br J Pharmacol. 2009 Dec;158(8):1911-21. doi: 10.1111/j.1476-5381.2009.00491.x.
The aim of this study was to investigate the effect of chronic treatment with antihypertensive and non-antihypertensive doses of zofenopril on cardiovascular changes in spontaneously hypertensive rats (SHR).
Male SHR were treated with 0.5 or 10 mg kg(-1) per day of zofenopril (Z(0.5) and Z(10)) for 3 months. SHR and Wistar-Kyoto rats (WKY) receiving vehicle were used as controls. Systolic blood pressure was measured using the tail cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. Angiotensin converting enzyme (ACE) activity was determined in plasma and tissues by a fluorimetric method. Vascular reactivity was evaluated on aortic rings by acetylcholine and sodium nitroprusside relaxations. Effects on vascular structure were assessed by lumen diameter, wall thickness and medial cross-sectional area determination. Superoxide anion generation was quantified using lucigenin-amplified chemiluminescence in aorta.
Long-term daily administration of zofenopril (10 mg kg(-1)) to SHR reduced blood pressure to WKY values, decreased cardiac hypertrophy, improved the acetylcholine-induced relaxant response and reversed the vascular remodelling. ACE inhibition and antioxidant activity were involved in these effects. 0.5 mg kg(-1) per day of zofenopril slightly modified blood pressure and the other effects were weaker.
Antihypertensive effects of chronic treatment with zofenopril were accompanied by recovery of endothelial function and improvement of cardiovascular structure. Low-dose zofenopril had little effect on blood pressure, with some benefits on cardiovascular structure and function. Inhibition of ACE and antioxidant activity were involved in these effects.
本研究旨在探讨长期应用抗高血压剂量和非抗高血压剂量佐芬普利对自发性高血压大鼠（SHR）心血管变化的影响。
雄性 SHR 分别给予 0.5 或 10mg/kg·d 的佐芬普利（Z(0.5)和 Z(10)）治疗 3 个月。同时设立 SHR 和 Wistar-Kyoto 大鼠（WKY）对照组，给予相应的溶剂。采用尾套法测量收缩压。左心室重量/体重比作为心肌肥厚指数。采用荧光法测定血浆和组织中血管紧张素转换酶（ACE）活性。通过乙酰胆碱和硝普钠诱导的血管舒张来评估血管反应性。通过测量管腔直径、管壁厚度和中膜横截面积来评估血管结构的变化。采用鲁米诺增强化学发光法测定主动脉中超氧阴离子的生成。
长期每日给予 SHR 佐芬普利（10mg/kg）可降低血压至 WKY 水平，减少心肌肥厚，改善乙酰胆碱诱导的舒张反应，并逆转血管重构。ACE 抑制和抗氧化活性参与了这些作用。每天 0.5mg/kg 的佐芬普利可轻度降低血压，其他作用较弱。
长期应用佐芬普利治疗具有抗高血压作用，同时伴有内皮功能的恢复和心血管结构的改善。低剂量佐芬普利对血压影响较小，但对心血管结构和功能有一定益处。ACE 抑制和抗氧化活性参与了这些作用。
