β受体阻滞剂对动脉粥样硬化家兔血管内皮依赖舒张功能的影响

Comparative effects of carvedilol,propranolol,and atenolol on nitric oxide-mediated endothelium-dependent vasorelaxation in atherosclerotic rabbits

目的:对比观察β受体阻滞剂卡维地洛、普萘洛尔与阿替洛尔对动脉粥样硬化家兔血管内皮舒张功能的影响。方法:30只雄兔随机分为高脂组、高脂加卡维地洛组(10mg.kg-1.d-1)、高脂加普萘洛尔组(10mg.kg-1.d-1)、高脂加阿替洛尔组(20mg.kg-1.d-1)和正常对照组。前4组给予相应处理1周后,行腹主动脉球囊损伤术,并继续相应处理10周;正常对照组给予假手术及正常饮食。干预结束时,测定血脂及一氧化氮(NO)水平,取动脉组织检测血管内皮依赖舒张功能、内皮源性NO释放量。结果:与正常对照组相比,高脂组血TC、TG、NO水平均明显升高,而内皮源性NO释放量均明显降低(均P<0.01)。与高脂组相比,3种β受体阻滞剂在所用剂量内均未对血脂产生显著性影响。卡维地洛明显升高内皮源性NO释放量1.6倍(P<0.05),而普萘洛尔与阿替洛尔均未对上述指标产生明显影响。与正常对照组相比,高脂组家兔血管内皮依赖舒张功能明显减弱(P<0.01),所用干预药物中,只有卡维地洛明显改善高脂家兔内皮依赖舒张功能(P<0.05)。结论:与普萘洛尔、阿替洛尔相比,卡维地洛更能增强内皮源性NO活性,改善NO介导血管内皮依赖舒张功能。

Objective：To compare the effects of carvedilol, propranolol, and atenolol on endothelium dependent vasorelaxation in rabbits with atherosclerosis, Method：Thirty rabbits were divided into the 5 groups： hyperlipidemic diet only （hyperlipidemic control, HC）, hyperlipidemic diet plused with propranolol （10 mg·kg^-1·d^-1）, atenolol （20 mg·kg^-1·d^-1）, carvedilol （10 mg·kg^-1·d^-1）, and normal control （NC） group. The ahead 4 groups underwent balloon injury and remained on their respective diets for 10 weeks. Rabbits in the NC group received sham operation and normal diet. At the end of the treatment, serum lipids and plasma nitric oxide（NO）, acetylcholine （ACh）-stimulated endothelium-derived NO release, ACh-induced endothelium-dependent relaxation were detected. Result： In HC group, total cholesterol, triglycerides and NO levels in plasma significantly increased, whereas ACh-stimulated NO release in aortic tissues decreased compared with those in NC group （all P〈0. 01 ）. Treatment with carvedilol, but not propranolol or atenolol, markedly increased ACh-stimulated NO release with 1.6 times （P〈0.05）. All of them did not have effect on serum lipids. Diastolic function depending on endothelial was diminished in HC group （8. 1±4.1）5 compared with normal control rabbits （55.1±2.2）% ,P〈50.01, and improved only in carvedilol-treated group（16.5±6.0）%, P〈0.05. Conclusion：This study suggests that carvedilol treatment would improve NO-mediated endothelial function in atherosclerotic rabbits. These beneficial effects of carvedilol are not shared by other β-blockers such as propranolol or atenolol.