氯沙坦、依那普利及其合用对腹主动脉缩窄型高血压大鼠的影响

Effects of Losartan, enalapril and their combination on hypertension with abdominal aorta binding in rats.

目的 探讨依那普利、氯沙坦及其合用对腹主动脉缩窄型高血压大鼠血压、心肌肥厚程度和心肌组织丝裂原活化蛋白激酶 (MAPK)的活性及表达的影响。方法 采用腹主动脉缩窄型高血压大鼠模型 ,然后将动物随机分为 7组 (n均 =6 )。分别为氯沙坦 (10 mg· kg- 1 · d- 1 )组 ,氯沙坦 (30 mg· kg- 1 · d- 1 )组 ,依那普利 (4mg· kg- 1 · d- 1 )组 ,依那普利 (12 mg· kg- 1· d- 1 )组 ,依那普利合用氯沙坦 (4m g· kg- 1· d- 1和 10 m g· kg- 1· d- 1 )组和安慰剂组。以假手术组作对照。给药 5周后测定左心室重量与体重比值、平滑肌肌动蛋白表达和 MAPK蛋白表达变化。结果 与假手术组比较 ,大鼠腹主动脉缩窄术后 6周血压明显升高 ,心肌组织发生明显肥厚 ,平滑肌肌动蛋白和 MAPK蛋白表达增高 (P<0 .0 1)。与安慰剂组比较 ,氯沙坦、依那普利及其合用可降低平均动脉血压 ,减轻心肌肥厚 ,同时降低平滑肌肌动蛋白和 MAPK蛋白表达 (P<0 .0 1) ,且氯沙坦、依那普利的作用呈剂量依赖性。与单用氯沙坦或依那普利比较 ,氯沙坦和依那普利合用可进一步降低平均动脉血压、减轻心肌肥厚和 MAPK蛋白表达 (P <0 .0 5 )。结论 MAPK是介导高血压心肌肥厚的重要信号分子。氯沙坦、依那普利均能减轻心肌肥厚和 MAPK蛋白?

Objective To investigate the effects of Losartan, enalapril and their combination on left ventricular hypertrophy and expression of mitogen activated protein kinase(MAPK) after hypertension with abdominal aorta binding in rats. Methods Thirty six rats with hypertension after abdominal aorta binding were randomly divided into 6 groups. (A) losartan(10mg·kg -1 ·d -1 ), (B). Losartan (30mg·kg -1 ·d -1 ), (C) enalapril (12mg·kg -1 ·d -1 ), (D) enalapril (4mg.kg -1 ·d -1 ), (E) concomitant losartan (10mg·kg -1 ·d -1 ) and enalapril (4mg·kg -1 ·d -1 ), and (F) placebo. Sham operated group were serve as controls. Losartan and enalapril were delivered by direct gastric gavage. After five weeks of treatment, the left ventricular weight /body weight, levels of smooth muscle actin and MAPK expression in each group were examined. Results Compared with sham operated rats, the mean blood pressure, cardiac weight, levers of smooth muscle actin and MAPK expression in the abdominal aorta binding groups were all significantly increased ( P <0.01). Compared with placebo group, the mean blood pressure, cardiac weight, levers of smooth muscle actin and MAPK expression were all significantly decreased ( P <0.01)in all five treatment groups( P <0.01). Losartan and enalapril exerted dose dependent. Compared with group A or D, the mean blood pressure, cardiac weight, levers of MAPK expression were decreased in group E( P <0.05). Conclusion The results indicated that MAPK may be involved in myocardial hypertrophy of hypertensive rat. Losartan, enalapril can decrease left ventricular hypertrophy and MAPK expression after hypertension with abdominal aorta binding in rats, and there is additive effect when the two drugs were used in combination.