复方利血平氨苯蝶啶片对离体胸主动脉血管环的舒张作用及机制研究

Vasorelaxant effect and mechanisms of compound reserpine and triamterene tablets on the isolated thoracic aorta rings

本研究主要评价复方利血平氨苯蝶啶片及其组分氨苯蝶啶对离体大鼠胸主动脉血管环的舒张作用,并探讨其作用机制。采用离体大鼠胸主动脉血管环模型,分别用高浓度KCl和去甲肾上腺素(norepinephrine,NE)预刺激,评价药物的舒张血管活性。通过各种工具药干预,观察药物舒张血管作用的内皮相关机制、钾通道相关机制和钙离子相关机制。动物福利和实验过程均遵循中国医学科学院药物研究所实验动物管理与动物福利伦理委员会审查要求。结果显示复方利血平氨苯蝶啶片和氨苯蝶啶均可以浓度依赖性舒张高钾和NE预收缩的血管环;氨苯蝶啶呈现出一定的内皮依赖性,N-硝基-L-精氨酸甲基酯(N-nitro-L-argininemethyl ester hydrochloride,L-NAME)在一定程度上影响其舒张作用,另外还可能与开放钙激活钾离子通道有关;复方利血平氨苯蝶啶片明显抑制由细胞内钙释放和外钙内流引起的血管收缩。总之,复方利血平氨苯蝶啶片和氨苯蝶啶在体外具有一定的舒张血管作用,复方利血平氨苯蝶啶片的舒张血管机制可能与内钙释放和外钙内流有关,氨苯蝶啶的舒张血管作用可能依赖于血管内皮功能,另外还可能与开放钙激活钾离子通道相关。

This study aimed to evaluate the vasorelaxant effect and mechanisms of compound reserpine and triamterene tablets(CRTTs)and its component triamterene on isolated rat thoracic aorta rings.Isolated rat thoracic aorta rings pre-contracted by high potassium or norepinephrine(NE)were used to evaluate the vasodilatory effect of CRTTs and its component triamterene.The mechanisms concerning endothelium,potassium channels and calcium channels were studied through the interventions of several tool drugs.Animal welfare and experimental procedures followed the requirements of the Laboratory Animal Management and Animal Welfare Ethics Committee of the Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College.The results showed that both CRTTs and triamterene had potent relaxant effect on KCl and NE precontracted vessels.Triamterene showed partial endothelium dependency,and N-nitro-L-argininemethyl ester hydrochloride(L-NAME)could influence the relaxant effect,which may be related to the opening of calciumactivated potassium channels.Meanwhile,CRTTs could inhibit intracellular Carelease and extracellular Cainflux.Overall,CRTTs and its component triamterene have vasorelaxant effects on vessels in vitro,and the vasorelaxant effect of CRTTs may be related to intracellular Carelease and extracellular Cainflux,while this effect of triamterene may depend on vascular endothelial function and may also be related to the opening of calcium-activated potassium channels.