摘要
目的:探讨具有钙拮抗及抗氧化作用的(7S,13R)-CPU86017及内皮素受体拮抗剂CPU0213对异丙肾上腺素诱导的血管功能损伤的改善作用。方法:将36只实验大鼠分为正常组、模型组、(7S,13R)-CPU86017和CPU0213治疗组,采用MedLab生物信号采集系统观察各组在去氧肾上腺素(1×10-6mol/L)预收缩血管后,乙酰胆碱梯度舒张大鼠离体主动脉环效应的变化;在L-硝基精氨酸或无L-硝基精氨酸孵育条件下,对去氧肾上腺素梯度加药引起的血管收缩效应;在含钙或无钙K-H液条件下,对去氧肾上腺素(1×10-6mol/L)引起的血管收缩变化及对KCl(100 mmol/L)引起的血管平滑肌收缩反应。结果:模型组对去氧肾上腺素、高钾的收缩反应增强,而对乙酰胆碱内皮依赖性舒张反应降低,NO的生物利用度明显降低。经(7S,13R)-CPU86017和CPU0213治疗后,血管功能得到显著改善。结论:异丙肾上腺素因损害血管内皮细胞功能而致血管活性异常。(7S,13R)-CPU86017及CPU0213可明显对抗此异常,改善血管功能。提示异丙肾上腺素引起β受体过度激活效应,可能由内皮素-1、氧自由基生成过多及钙通道的过度激活所介导。
Objective: To study the intervention of (7 S, 13 R)-CPU86017 and CPU0213 on isoproterenolinduced damage to vascular function. Methods: 36 rats were randomly divided into four groups: the normal, the isoproterenol model, (7S, 13R)-CPU86017 and CPU0213 group. Changes of tension of rat thoracic aortic rings were measured by MedLab biologic signal collection system. The relaxation effect was observed in the isolated rat rings pretreated by phenylephrine ( 1 × 10^-6 mol/L), and the response to phenylephrine (1×10^-9- 1 ×10^-5 mol/L) induced artery contraction in the presence or absence of NO-L-Arg was measured separately. Vaso-contraction of the rings induced by phenylephrine ( 1×10^-6 mol/L) or by adding KCl( 100 mmol/L) under the Ca^2+-contained and Ca^2+-free K-H solution was observed. Results: The constriction responses of thoracic aortic rings to phenylephrine and KCl( 100 mmol/L) were enhanced and the relaxation response to Ach was depressed significantly in the model group. This effect was partly reversed by CPU0213 and (7S, 13R)-CPU86017. The NO bioavailability was significantly reduced in the model group relative to the normal, but remarkably improved after the treatment of CPU0213 and (7 S, 13 R)-CPU86017. Conclusion: These findings suggest that vascular damage induced by isoproterenol is due to an impaired function of vascular endothelium ceil. CPU0213 and (7S, 13R )-CPU86017 can obviously intervene isoproterenol-induced damage to vasculature and improve vascular function. This indicates that isoproterenol- induced over-activation of the beta receptors might be mediated by an increase in endothelin-1, reactive oxygen species and over-activated Ca^2+ channels.
出处
《药学进展》
CAS
2007年第2期68-73,共6页
Progress in Pharmaceutical Sciences
基金
江苏省自然科学基金资助项目(No.BK2002120)