艾力沙坦钾单次给药对自发性高血压大鼠血压的影响

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 hypertensirerats，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1d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（systolicblood pressure，SBP），舒张压（diastolic blood pressure，DBP）和心动间期（heart period，HP）。记录给药前1h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 cellulose，CMC-Na）、艾力沙坦酯（allisartan，ALS-3）2．5mg／kg、氯沙坦钾（losartan potassium，Los）2．5mg／kg和受试药品ALS3K各1．0、2．5、5．0、10mg／kg；给药后连续记录6hSBP、DBP和HP的变化。结果ALS3K在2．5mg／kg剂量开始明显降压，与给药前比较，SBP和DBP分别下降15、16mmHg（P〈0．01）；ALS3K5．0和10mg／kg降压效果与2．5mg／kg相近；各剂量对HP没有明显的影响。ALS-3以及Los在2．5mg／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。

Effect of a single dose of ALS3K on blood pressure in spontaneously hypertensive rats

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 O. 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.