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作 者:苏丹[1] 马春来[1] 吴大正[1] 周吉燕[1] 胡之璧[1]
出 处:《中国新药与临床杂志》2006年第5期353-358,共6页Chinese Journal of New Drugs and Clinical Remedies
摘 要:目的:应用氯沙坦和雷米普利来探讨血管紧张肽Ⅱ对压力过载引起的左心室肥厚的相关作用。方法:采用缩窄大鼠肾动脉间腹主动脉的方法造成后负荷过载所致的左心室肥厚模型。造模后12 wk,分别给予灌服氯沙坦(1.0 mg·kg^(-1))和雷米普利(1.0 mg·kg^(-1))。给药12 wk后,应用形态测量学测定左室重量指数;Langendorff离体心脏灌流法测定离体心功能和右颈总动脉插管法测定在体心功能及血流动力学;应用酶联免疫吸附法测定大鼠血浆血管紧张肽Ⅱ(AngⅡ)、醛甾(固)酮(Ald)含量和心肌组织AngⅡ含量。结果:与模型动物比较,氯沙坦和雷米普利均能降低左室重量指数;在体大鼠血流动力学的测定中发现,压力过载造成大鼠动脉血压和左室收缩压显著升高,应用氯沙坦和雷米普利治疗后,明显改善大鼠心脏收缩功能,降低左室收缩压和外周动脉血压;离体大鼠心功能测定发现,压力过载引起离体大鼠心脏左室舒张压和左室最大上升速率下降,氯沙坦和雷米普利不能改善左室舒张压和左室最大上升速率下降。此外,氯沙坦和雷米普利能够降低心室重构过程中血浆和心肌组织中AngⅡ的含量以及血浆中Ald含量。结论:应用氯沙坦和雷米普利均能够降低缩窄大鼠腹主动脉造成的左心室肥厚,进一步提示AngⅡ在慢性压力过载导致左心室重构中起着关键性作用。AIM: To observe the correlation between angiotensin Ⅱ (Ang Ⅱ) and left ventricular pressure overload hypertrophy and the cardioprotective effects of ramipril and losartan. METHODS: Left ventriclar pressure overload hypertrophy in rats was produced by abdominal aorta banding between bilateral renal aortas for 12 weeks. Rats received distilled water (2 mL) or ramipril (1.0 mg·kg^-1) or losartan (10 mg·kg^-1) respectively for 12 weeks. The left ventricular mass index(LVMI) was calculated by morphometry methods. Cardiac function was measured by the method of isolated perfused heart according to Langendorff technique in vitro. Hemodynamics and cardiac function were assessed by the way of right common carotid artery cannula in vivo. The contents of Ang Ⅱ and aldosterone (Aid) in plasma and Ang Ⅱ in myocardial tissue were tested by ELISA. RESULTS: LVMI in ramipril and losartan treated groups were significantly greater than that in vehicle-treated group. Systolic arterial pressure, diastolic arterial pressure and left ventricle systolic pressure decreased significantly (P 〈 0.01) in ramipril and losartan treated group in vivo. Compared with vehicle-treated group, there was no significant difference of left ventricular developed pressure and the maximum rising rate treated with ramipril and losartan. The content of Ang Ⅱ in plasma and Ang Ⅱ and Aid in myocardial tissue was lower (P 〈 0.05) than that in vehicletreated group. CONCLUSION: Both ramipril and losartan can improve the left ventricular pressure overload hypertrophy and Ang Ⅱ plays a principal role in the LV remodeling in response to chronic pressure overload.
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