利尿剂协同ACE抑制剂降压作用的实验研究

Synergism of diuretic and ACE inhibitor on the reduction of blood pressure:Experimental study

目的研究利尿剂氢氯噻嗪与ACE抑制剂依那普利联合对自发性高血压大鼠降低血压及血压波动性的协同作用,评价两药不同比例配伍时的协同作用效果。方法采用清醒动物血压监测技术,监测自发性高血压大鼠分别通过胃瘘管给予0.8%的羧甲基纤维素钠(CMC)、氢氯噻嗪(10mg/kg)、依那普利(2,4,8mg/kg)、氢氯噻嗪和依那普利混悬液(10+2、10+4、10+8mg/kg)后血压及血压波动性的变化。结果与对照组比较氢氯噻嗪和依那普利合用时可以明显的降低血压及血压波动性。大剂量合用时降低收缩压55mmHg(1mmHg=0.133kPa),大于两药单独使用时的降压幅度。q值在氢氯噻嗪+依那普利10+4mg/kg时最大。结论利尿剂与ACE抑制剂合用对降低血压及血压波动性具有明显的协同作用,氢氯噻嗪:依那普利为5:2时协同作用最为明显。

Objective To investigate the possible synergism of hydrochlorothiazide and enalapril on reducing both blood pressure （BP） and blood pressure variability （BPV） in spontaneously hypertensive rats （SHR）. Method Eighty animals were randomly divided into eight groups. The doses were 10 mg/kg for hydroehlorothiazide, 2, 4, and 8 mg/kg for enalapril respectively, and 10＋2, 10＋4, 10＋8 mg/kg for the combination of these two drugs and 0.8% carboxymethyleellulose as control. The drugs were given via a catheter of gastric fistula. BP was then continuously recorded for 5 hours from 1 hour before drug administration to the end of 4th hour after drug administration, in conscious and freely moving rats. Results The effects on both BP and BPV reduction of the combination of hydrochlorothiazide and enalapril were greater than the alone drug in SHR. The two drugs possessed an obvious synergism on both systolic blood pressure （SBP） and systolic blood pressure variability （SBPV） reduction with small dose in SHR. Conclusion There is a significant synergistic effect of hydroehlorothiazide combined with enalapril on lowering and stabilizing BP in SHR, which the effect at 5：2 （hydroehlorothiazide/enalapril） is the most significant.