亚降压剂量雷米普利预防高血压心肌肥厚的机制

Mechanism involved in the prevention of sub hypotensive dose of ramipril on hypertensive cardiac hypertrophy of rat

目的 探讨亚降压剂量雷米普利的抗氧化作用对其抗高血压心肌肥厚作用的影响。方法 采用腹主动脉缩窄法制备大鼠高血压心肌肥厚模型。观察一氧化氮合酶抑制剂ＮＬ精氨酸（６ｍｇ·ｋｇ－１·ｄ－１）和ＶｉｔＥ（２００Ｕ·ｄ－１）对雷米普利（１００μｇ·ｋｇ－１·ｄ－１）抗心肌肥厚的影响，以及心肌超氧化物歧化酶（ＳＯＤ）、一氧化氮代谢物（ＮＯ２－）等指标的变化。结果 给予雷米普利后８ｗｋ，与对照组比较心肌肥厚减轻而血压无明显降低，ＮＯ２－含量和ＳＯＤ活性明显提高，脂质过氧化物减少。ＶｉｔＥ能增强上述大部分作用，而ＮＬ精氨酸能逆转此增强作用。结论 亚降压剂量雷米普利有抗心肌肥厚的作用，ＶｉｔＥ对此有增强作用，其机制与增强心肌抗氧化能力有关。

Aim To examine the role of antioxidant effect of subhypotensive dose of ACE inhibitor ramipril in its anti hypertrophic effect in rat myocardium. METHODS Model of hypertension induced myocardial hypertrophy of rat was reproduced by coarctation of abdominal aorta. The effects of nitric oxide (NO) synthase inhibitor N L arginine (6 mg·kg -1 ·d -1 ) and Vitamin E(200 U·d -1 ) on cardiac hypertrophy were examined. The change of superoxide dismutase (SOD) and NO production (assayed as NO 2 -) were monitored. RESULTS The myocardial hypertrophy was effectively prevented under hypertensive condition after treatment with ramipril for 8 week, while SOD activity and NO 2 - content were significantly increased and lipid peroxidation was significantly attenuated. Vitamin E enhanced ramipril effect and N L arginine reversed its benficail effects. CONCLUSION These data showed that sub hypotensive dose of ramipril and in combination with vitamin E enhances myocardial antioxidative capability and NO release, which plays an important role in the mechanism of action involved in their antihypertensive cardiac hypertrophic effects.