三种降压药单用及联用对肾性高血压大鼠左心室肥厚及离子泵活性的影响

Effect of enalapril,irbesartan and amlodipine used alone or in combination on LVH and ion pump activity in rats with renal hypertension

目的探讨依那普利、厄贝沙坦和氨氯地平单用及联用改善肾性高血压大鼠(RHR)左心室肥厚(LVH)的疗效及对左心室肌离子泵活性的影响。方法 42只大鼠用两肾一夹制造RHR模型,随机分为模型组、依那普利组[10 mg/(kg·d)]、厄贝沙坦组[50 mg/(kg·d)]、氨氯地平组[5 mg/(kg·d)]和联合用药3组(依厄组、依氨组、厄氨组),每组6只;另6只为假手术组。测大鼠术前、术后血压,用药6周后,测大鼠左心室重量指数(LVMI),HE染色观察左心室病理变化,用生物酶学方法测左心室肌钠泵、钙泵活性。结果与假手术组比较,模型组收缩压和LVMI显著增高,左心室离子泵活性降低(P<0.01);与模型组比较,各用药组收缩压和LVMI明显降低(P<0.01),氨氯地平组收缩压和LVMI明显高于其他用药组(P<0.05)。结论 RHR单用依那普利、厄贝沙坦的降压及逆转LVH作用优于单用氨氯地平;3种降压药均能增加左心室肌离子泵活性,联合用药无明显协同作用。

Objective To study the effect of enalapril,irbesartan and amlodipine used alone or in combination on LVH and ion pump activity in rats with renal hypertension. Methods A rat renal hypertension model was established with two-kidney-one clip method. Forty-two rats were randomly divided into model group, enalapril group[-10 mg/（kg . d） ], irbesartan group[50 mg/（kg . d） ], amlodipine group[ 5 mg/（kg . d） ], enalapril ＋ irbesartan group, enalapril ＋ amlodipine group, irbesartan＋amlodipine group,6 in each group. Another 6 rats served as a sham operation group. Their blood pressures were measured before and after operation, their LVMI was assayed. Six weeks after drug treatment, left ventricle lesions were observed with HE staining, left ventricle sodium and calcium pump activities were detected by biological and enzymologic methods. Results The systolic pressure and LVMI were significantly higher while the left ventricle ion pump activities were significantly lower in model group than in sham operation group（P〈0.01） ,and significantly lower in drug treatment groups than in model group （P〈0.01）while significantly higher in amlodipine group than in other groups 6 weeks after drug treatment（P〈0.05）. Conclusion The effect of enalapril or irbesartan used alone on LVH and hypertension is better than amlodipine used alone. Their combination can increase the ion pump activities in left ventricles but has no synergistic effects on renal hypertension in rats.