摘要:
目的: 本实验通过观察艾力沙坦钾(allisartan potassium,ALS3K)对自发性高血压大鼠(spontaneously hyperten-sive rats,SHR)单次给药前后血压变化的情况,研究艾力沙坦钾对SHR的降压作用及量效关系。 方法: SHR随机分为7个组,每组9只。SHR麻醉状态下行股动脉插管并造胃瘘管,恢复1 d后,动物在清醒自由活动状态下,由计算机连续记录每搏收缩压(systolic blood pressure,SBP),舒张压(diastolic blood pressure,DBP)和心动间期(heart period,HP)。记录给药前1 h内血压和心动间期作为给药前基础值。然后每组SHR经胃瘘管分别给予0.5%的羧甲基纤维素钠(sodium carboxymathyl cellu-lose,CMC-Na)、艾力沙坦酯(allisartan,ALS-3)2.5 mg/kg、氯沙坦钾(losartan potassium,Los)2.5 mg/kg和受试药品ALS3K各1.0、2.5、5.0、10 mg/kg;给药后连续记录6 h SBP、DBP和HP的变化。 结果: ALS3K在2.5 mg/kg剂量开始明显降压,与给药前比较,SBP和DBP分别下降15、16 mmHg(P<0.01);ALS3K 5.0和10 mg/kg降压效果与2.5 mg/kg相近;各剂量对HP没有明显的影响。ALS-3以及Los在2.5 mg/kg给药剂量下无明显的降压作用。 结论: ALS3K单次给药能平稳持久地降低SHR的血压,在一定剂量范围内有较好的量效关系。经过结构改造,ALS3K可以通过更低的给药剂量而获得比ALS-3更好的降压疗效。
Abstract:
Objective To investigate the effect of a single dose of allisartan potassium(ALS3K) on the blood pressure(BP) in spontaneously hypertensive rats(SHR). Methods SHR were randomly divided into seven groups(n=9 per group) and given 0.5%CMC-Na,allisartan 2.5 mg/kg,Losartan potassium 2.5 mg/kg,ALS3K 1.0、2.5、5.0 and 10 mg/kg,respectively.Rats were anesthetized and two catheters were inserted into the lower abdominal aorta via the left femoral artery and the stomach.After 24 h recovery period,the drugs were dissolved in 0.5 % carboxymethylcellulose sodium(CMC) and given via a catheter inserted into the stomach.The BP and HP 1 h before drug administration and 6 h after drug administration were determined in conscious freely moving SHR by computer. Results Compared to before administration,the BP was significantly decreased by ALS3K at the dose of 2.5 mg/kg(SBP/DBP,15/16 mmHg,(P<0.01).Similar Results were found by ALS3K at the dose of 5.0 and 10 mg/kg.The BP had no change in ALS-3(2.5 mg/kg) and Los(2.5 mg/kg) treatment groups.HP had no change in any groups. Conclusion Compared with the basal values,levels of SBP and DBP after drug administration were significantly decreased dose-dependently by ALS3K.In the way of changing the structure,SHR can be given lower dose by ALS3K to get the same BP reduction as ALS-3.
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