Synergism of amlodipine and candesartan on blood pressure reduction and organ protection in hypertensive rats
Synergism of amlodipine and candesartan on blood pressure reduction and organ protection in hypertensive rats
复制标题
氨氯地平与坎地沙坦对高血压大鼠降压及器官保护的协同作用
DOI：
10.1111/1440-1681.12901
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发表时间：
2018-06-01
影响因子：
2.9
通讯作者：
Liu, Ai-Jun
中科院分区：
文献类型：
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作者：
Cheng, Yan-Qiong;Tan, Bing-Yi;Liu, Ai-Jun
本研究旨在探讨氨氯地平和坎地沙坦对高血压大鼠降压作用的可能协同作用。观察末梢脏器保护情况。在急性实验中，给自发性高血压大鼠(SHR)灌胃给予氨氯地平(0.5、1、2、2、3 mg/kg)和坎地沙坦(1、2、3、4、6、8 mg/kg)以及14种不同的组合，以寻找协同作用的可能比例。在两肾一夹(2K1C)大鼠模型上，观察氨氯地平(1 mg/kg)、卡地拉坦(2 mg/kg)及其合用的降压作用。慢性应用氨氯地平(1 mg/kg)、坎地沙坦(2 mg/kg)及二者联合治疗5个月。记录血压后进行脏器损害评估。用概率和检验(Q检验)评价其协同作用。氨氯地平与坎地沙坦具有协同降压作用。最佳剂量比为1：2。2K1C高血压大鼠也证实了其协同作用。在慢性研究中，该药(1：2)在降低血压及血压变异性(BPV)和保护末梢器官方面具有明显的协同作用。多元回归分析显示，心脏、主动脉肥厚指数和肾小球损伤参数与BP、BPV呈正相关。综上所述，氨氯地平与坎地沙坦合用具有较强的降压作用，对高血压的降压和器官保护有明显的协同作用。最佳比例为1：2。BP和BPV的降低可能都对终末器官保护有重要作用。
This study was designed to investigate the possible synergism of amlodipine and candesartan on the reduction of blood pressure (BP) in hypertensive rats. The end organ protection was also observed. In acute experiment, spontaneously hypertensive rats (SHRs) were treated with intragastric administration of amlodipine (0.5, 1, 2, 3 mg/kg), candesartan (1, 2, 3, 4, 6, 8 mg/kg), and 14 different combinations to find the possible ratio of synergistic interaction. In two kidneys, one clip (2K1C) rats, the effects of amlodipine (1 mg/kg), canderastan (2 mg/kg) and their combination on BP reduction were also observed. In chronic study, SHRs were treated with amlodipine (1 mg/kg), candesartan (2 mg/kg), and their combination for 5 months. Organ damage evaluation was performed after BP recording. The probability sum test (q test) was used to evaluate the synergistic action. There is a synergistic interaction between amlodipine and candesartan on BP reduction. The optimal dose ratio is 1:2. The synergistic effect was also confirmed by 2K1C hypertensive rats. In chronic study, this combination (1:2) possessed an obvious synergism on the reduction of BP and BP variability (BPV) and protection on end organs. Multiple regression analysis showed that heart and aortic hypertrophy indexes and glomerular damage parameters were positively related to BP and BPV. In conclusion, combination of amlodipine and candesartan exhibited a potent antihypertensive effect and possessed an obvious synergism on BP reduction and organ protection in hypertension. The optimal proportion was 1:2. BP and BPV reduction may both importantly contribute to end organ protection.