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目的探讨依那普利、厄贝沙坦、氨氯地平单用及两者联用等不同治疗方案对肾血管性高血压大鼠左心室肥厚和左心室肾素血管紧张素醛固酮系统的影响。方法选用8～12周雄性Sprague Dawley(SD)大鼠,采用两肾一夹制成肾血管性高血压大鼠模型,随机分为假手术组、模型组、依那普利组、厄贝沙坦组、氨氯地平组、依那普利+氨氯地平组、依那普利+厄贝沙坦组和厄贝沙坦+氨氯地平组,每组6只。测量各组大鼠术前、术后血压,用药6周后,测量大鼠左心室质量指数(LVMI),采用放射免疫法检测心室肾素活性、血管紧张素Ⅱ(AngⅡ)、醛固酮水平及血浆AngⅡ水平,Real-time PCR测定左心室组织AngⅡ1型受体(AT1R)和2型受体(AT2R)mRNA表达。结果所有用药组均能明显降低血压和LVMI,且依那普利+氨氯地平及厄贝沙坦+氨氯地平的效应大于对应单药的效应之和,具有协同效应(P<0.01)。除单用氨氯地平外,其他用药组均能降低血浆AngⅡ水平,且所有联合用药均具有协同效应[依那普利+厄贝沙坦组(190.70±89.38)、依那普利+氨氯地平组(221.08±67.28)、厄贝沙坦+氨氯地平组(589.22±85.81),比依那普利组(319.75±91.46)、厄贝沙坦组(799.34±198.88)、氨氯地平组(1414.00±130.42)pg/mL;均P<0.01]。所有用药组均能抑制肾素活性,且所有联合用药均具有协同效应(P<0.01)。除单用厄贝沙坦及厄贝沙坦+氨氯地平外,其他用药组均能降低左心室AngⅡ水平;单用厄贝沙坦及厄贝沙坦+氨氯地平可引起左心室醛固酮水平升高(P<0.01)。所有用药组均能下调AT1RmRNA表达,依那普利+氨氯地平具有协同效应(P<0.01);单用厄贝沙坦可上调AT2RmRNA表达;除单用氨氯地平外,其他用药组均能升高AT2R/AT1R,依那普利+氨氯地平具有协同效应(P<0.01)。结论氨氯地平联合依那普利或厄贝沙坦具有协同降血压和逆转左心室肥厚作用;依那普利联合氨氯地平在降低AngⅡ水平、抑制左心室肾素活性、下调AT1RmRNA表达及升高AT2R/AT1R方面具有协同效应。
Objective To investigate the effects of enalapril, irbesartan, amlodipine and their combination therapy on left ventricular hypertrophy and left ventricular renin-angiotensin aldosterone system in renovascular hypertensive rats. Methods Male Sprague Dawley rats (8-12 weeks old) were randomly divided into sham-operation group, model group, enalapril-treated group, Amlodipine group, amlodipine + amlodipine group, enalapril + irbesartan group and irbesartan + amlodipine group, with 6 rats in each group. The preoperative and postoperative blood pressure were measured in each group. After 6 weeks of treatment, the left ventricular mass index (LVMI) of rats were measured. The ventricular renin activity, angiotensin Ⅱ (AngⅡ), aldosterone level and plasma The levels of Ang Ⅱ and AT2R in left ventricular tissue were detected by Real-time PCR. Results All the treatment groups were able to significantly lower blood pressure and LVMI, and the effects of enalapril + amlodipine and irbesartan + amlodipine were greater than those of the corresponding monotherapy, with synergistic effects (P <0.01). Except for amlodipine alone, all the other drugs could reduce plasma AngⅡ level, and all the combination therapy had synergistic effects [enalapril + irbesartan group (190.70 ± 89.38), enalapril + (221.08 ± 67.28), irbesartan + amlodipine group (589.22 ± 85.81), enalapril group (319.75 ± 91.46), irbesartan group (799.34 ± 198.88), amlodipine group (1414.00 ± 130.42) pg / mL, all P <0.01]. All treatment groups were able to inhibit renin activity, and all combinations had synergistic effects (P <0.01). In addition to irbesartan alone and irbesartan + amlodipine, other treatment groups can reduce the level of left ventricular AngⅡ; irbesartan and irbesartan alone amlodipine can cause left ventricular aldosterone levels Increased (P <0.01). All the treatment groups could down-regulate the expression of AT1R mRNA, and enalapril + amlodipine had a synergistic effect (P <0.01). The treatment with irbesartan alone could up-regulate the expression of AT2R mRNA. Except for amlodipine alone, Elevated AT2R / AT1R, enalapril + amlodipine have a synergistic effect (P <0.01). Conclusions Amlodipine combined with enalapril or irbesartan can reduce blood pressure and reverse left ventricular hypertrophy. Enalapril combined with amlodipine can decrease the level of AngⅡ, inhibit the activity of left ventricle renin, and down-regulate the expression of AT1R mRNA High AT2R / AT1R aspects have a synergistic effect.