Su Ding-feng, Xu Li-ping, Miao Chao-yu, Xie He-hui, Shen Fu-ming, Jiang Yuan-ying
Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
Acta Pharmacol Sin. 2004 Feb;25(2):148-51.
Computerized analysis of blood pressure in conscious freely moving rats is a sound technique for physiological and pharmacological studies. The present work, based on this technique, was designed to introduce two useful methods for the evaluation of antihypertensive drugs in conscious spontaneously hypertensive rat (SHR). They were the directly intragastric administration of drugs and modified probability sum test for evaluating the synergism of the combination of two drugs.
(1) Directly intragastric administration was used in conscious rats. A catheter was inserted into stomach immediately after arterial catheter insertion. Three days after operation, blood pressure was recorded and drug might be given intragastrically via the gastric catheter. (2) Modified probability sum test was used to evaluate the synergism of two drugs. The formula was: q=P(A+B)/(PA+PB-PAxB). With this method, it was obtained: q=1.32 for the effects of the combination of atenolol and nitrendipine (20 mg/kg+10 mg/kg) on systolic blood pressure; q=1.41 for the effects of the combination of atenolol and amlodipine (10 mg/kg+1 mg/kg) on systolic blood pressure.
The two methods introduced by the present work will be important and useful for antihypertensive drug evaluation in conscious freely moving rats.
对清醒自由活动大鼠的血压进行计算机化分析是一种用于生理和药理研究的可靠技术。基于该技术,本研究旨在介绍两种在清醒自发性高血压大鼠(SHR)中评估抗高血压药物的有用方法。它们分别是药物直接灌胃给药法以及用于评估两种药物联合协同作用的改良概率和检验法。
(1)在清醒大鼠中采用直接灌胃给药法。在插入动脉导管后立即插入一根胃导管。术后三天记录血压,并可通过胃导管对大鼠进行灌胃给药。(2)采用改良概率和检验法评估两种药物的协同作用。公式为:q = P(A + B)/(PA + PB - PA×B)。用该方法得出:阿替洛尔与尼群地平(20毫克/千克 + 10毫克/千克)联合使用对收缩压的影响,q = 1.32;阿替洛尔与氨氯地平(10毫克/千克 + 1毫克/千克)联合使用对收缩压的影响,q = 1.41。
本研究介绍的这两种方法对于在清醒自由活动大鼠中评估抗高血压药物具有重要意义且十分有用。