新型AT_1受体拮抗剂Ⅰb对血管紧张素Ⅱ的拮抗作用  

Inhibition effects of a new angiotensin type 1 receptor antagonist Ⅰb on angiotensin Ⅱ

作　　者：王玉[1] 王秋娟[1] 吴锦慧[1] 徐进宜[2] 吴晓明[2] 

机构地区：[1]中国药科大学生理学教研室,南京210009 [2]中国药科大学药物化学教研室,南京210009

出　　处：《中国药科大学学报》2007年第1期69-72,共4页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.130371688);教育部重点基金资助项目(No.103089)~~

摘　　要：目的:研究新型AT1受体拮抗剂Ⅰb对血管紧张素Ⅱ(AngⅡ)的拮抗作用。方法:采用放射性受体配体分析法、家兔离体主动脉环法以及大鼠静脉输注AngⅡ测定血压变化的方法,评价Ⅰb对AngⅡ的拮抗作用。结果:Ⅰb剂量相关性抑制125I-AngⅡ与血管平滑肌细胞膜AT1受体的结合,IC50为0.96nmol/L;Ⅰb(1×10-8.5,1×10-8,1×10-7.5mol/L)可以使AngⅡ的浓度效应曲线向右移动的同时也使最大效应降低,减活指数pD2′为7.29;预先静脉推注化合物Ⅰb(0.01,0.1,1mg/kg)后,AngⅡ的浓度效应曲线右移,ED50分别为1.6μg/kg,1.9μg/kg和2.7μg/kg。结论:化合物Ⅰb对AngⅡ有显著的拮抗作用。Aim： To study the inhibition of Angiotensin Ⅱ （Ang Ⅱ） response by I b, a new angiotensin type 1 （AT1） receptor antagonist. Methods： Competitive mdioligand binding assay, isolated rabbit thoracic aorta tings and pithed Ang Ⅱ -challenged rats were used to evaluate the antagonistic effects of Ⅰ b. Results： Ⅰ b could inhibit the binding of ^125Ⅰ-Ang Ⅱ to ATI receptor on vascular smooth muscle cell in a dose-dependent maimer with IC50 value of 0.96 nmol/L. Ⅰ b（ 1 × 10^-8.5,1 × 10^-8, 1 × 10^-7.5 mol/L）produced a rightward shift in the concentration-response curve for AngⅡ with a change in the maximal contractile response and the pD2＇ was 7.29. Pretreated with Ⅰ b （0.01,0.1,1 mg/kg）, the concentration-response curve of AngⅡshifted to the right. The corresponding ED50 of Ang Ⅱ was 1.6 μg/kg, 1.9 μg/kg and 2.7 μg/kg, respectively. Conclusion： Ⅰ b has significant antagonism to Ang Ⅱ .

关 键 词：AT1受体拮抗剂 Ⅰb 放射性配体受体分析 离体血管 血压 

分 类 号：R96[医药卫生—药理学]