长期服用氨酰心安对大鼠心脏肾上腺素受体的影响  

Effects of Long-term Atenolol Treatment on Cardiac Adrenoreceptors in Rats

作　　者：高大中[1] 殷耀辉[1] 佘强[1] 刘东[1] 李增高[1] 

机构地区：[1]重庆医科大学附属第二医院心内科,重庆市400010

出　　处：《中国药房》2001年第9期524-527,共4页China Pharmacy

摘　　要：目的：了解心脏病患者长期服用β－受体桔抗剂后，心功能究竟能否得到改善。方法：给大鼠服用选择性β１－受体桔抗剂氨酰心安１２ｗｋ后，采用放射配体结合实验和离体左心房收缩功能实验，观察大鼠心脏β－受体及其亚型和α１－受体的数量、分布以及左心房收缩功能的改变。结果：长期服用氨酰心安后心脏α１－受体、总β－受体的密度和β１－受体、β２－受体亚型所占β－受体总数的比例均无明显改变。但氨酰心安组左心房异丙肾上腺素的浓度－收缩效应曲线较对照组明显左移。氨酰心安组的选择性β１－受体桔抗剂 ＣＧＰ２０７１２Ａ桔抗异丙肾上腺素介导的正性变力效应的 ＰＡ２值显著大于对照组；而 ＩＣＩ １１８５５１桔抗异丙肾上腺素的ＰＫＢ值在两组间无显著性差异。用高效液相色谱法测定氨酰心安组血浆氨酰心安浓度为３．５ｕｍｏｌ／Ｌ，血浆中去甲肾上腺素水平两组间无显著性区别，但氨酰心安组血浆肾上腺素水平明显低于对照组。结论：长期服用β１－受体桔抗剂后，心脏β－受体对激动剂异丙肾上腺素的敏感性明显增强，且以β１－受体的敏感性增强更为显著。但β－受体及其亚型的受体数目并无明显改变。此外，长期服用β１－受体桔抗剂后，服用氨酰心安组大鼠的血浆肾上腺素水平明显低于对照?PURPOSE: To know whether the cardiac function of the patients with heart disease is impaired or improved after long-term taking β-AR antagonists. METHODS: After giving the rats β-AR selective antagonist, atenolol, for 12wk, the method of radioligand binding assay and the experiment of isolated left-atrium contractive function were carried out to observe the quantity and distribution of β-AR, its subtypes, α-AR, and the change of left - atrium contractive function. RESULTS: After long-term administration of atenolol, there were no any obvious changes in α-AR, the density of the total β-AR, β1-AR, and the proportion of β2-AR in tota1 amount of β-AR, but the con centrat ion - response cu rves shi fted l e ftwa rd s si gn ifi cant ly as compared with control group- The PA2 value of isoprotenol(ISO) - induced positive inotropic effect after antagonized by β1-AR selective antagonist CGP20712A in atenolol group was increased significantly as compared with control group. But the PKB value after antagonized by ICI 118511 showed no obvious difference between two groups. HPLC detection showed that the level of plasma atenolol was 3. 5pmol/L in atenolol group and the leveIs of plasma norepinephrine had no significant difference between two groups. But the level of plasma adrenaline in atenolol group was obviously lower than that in control group. CONCLUSIO- N: The long-term administration of βl-AR antagonist will cause significant increase of the sensitivity of heart β-AR, especially β1-AR to excitant ISO. But the number of β-AR and its subtypes did not change significantly. Besides, after the long-term administration of β1-AR antagonist atenolol, the level of plasma adrenaline in rats was much lower than that in control group.

关 键 词：氨酰心安 Β-肾上腺素受体 大鼠心脏 受体亚型 

分 类 号：R965.1[医药卫生—药理学] R966[医药卫生—药学]