钙通道开放剂

近年来对钾通道的研究已认识到K^+诱导的血管舒张作用与钾通道开放有关。新降压药吡那地尔(Pinacidil)的主要作用机制是开放钾通道,已进入Ⅲ期临床试验。该药已在丹麦批准应用,欧、美等一些国家也进行了试用。本类药物是有发展前途的新型降压药物。吡那地尔(pinacidil,pindac,P1134) 吡那地尔是氰胍衍生物,为本类的代表药。化学名为〔N″-氰基-N-吡啶基-N′-1,2,2-三甲基-正丙基胍〕。药理 1.钾通道开放作用Weston等报道,在大鼠门静脉和主动脉实验中,0.

钾通道开放剂预处理对兔离体基底动脉缺氧-复氧损伤的保护作用

目的:观察ATP敏感性钾通道开放剂吡那地尔(pinacidil)和钙激活钾通道开放剂NS1619对基底动脉缺氧复氧(H/R)损伤的保护能力。方法:采用离体血管环灌流的方法,比较对照组、缺氧复氧组、吡那地尔预处理组和NS1619预处理组4组血管环对缩血管物质U46619(前列腺素A_2模拟物)及内皮依赖性扩血管物质乙酰胆碱(ACh)以及非内皮依赖性扩血管物质硝普钠(SNP)的反应。结果:①H/R组与对照组比较,兔基底动脉对U46619的反应明显增强,对SNP的反应未见差异,而对ACh的反应明显减弱;②经吡那地尔和NS1619分别预处理后,可以预防离休兔基底动脉在缺氧复氧后对ACh舒张作用的减弱和对U46619收缩反应的增强。结论:吡那地尔和NS1619分别预处理后可以保护基底动脉内皮细胞免受后继H/R的损伤。

急性心力衰竭症候群相关药物治疗进展

急性心力衰竭症候群患者耗费了大量的医疗资源,对其本人、家庭和社会带来了巨大的经济负担。在传统药物基础上,利钠肽、醛固酮受体拮抗剂、钙增敏及钾通道开放剂、内皮素和血管加压素拮抗剂等新药的应用对于这类患者治疗疗效的提高引起了广泛的关注。现对此作一简单介绍。

Protective effect and mechanism of K_(ATp) channel opener on the sinoatrial node cells of neonatal rat cultured in simulated ischemia-reperfusion

Objective: To study the effect of KATp channel opener and its possible mechanism on the sinoatrial node cells of neonatal rats which were cultured under simulated ischemia-reperfusion. Methods: Freshly isolated sinoatrial node (SAN) cells of neonatal rats were purified and cultured for 2 d, and then they were randomly divided into the control, simulated ischemia-reperfusion group (I/R group) , group intervened with KATp channel opener pinacidil (P + I/R group), KATP Channel blocking agent 5-HD (5-HD + I/R group) , and group with the 2 agents at same time (5-HD + P + I/R group) . The survival rate of cells was measured by flow cytometry and the content of intracellular calcium in the cells of each group was detected with laser confocal microscopy. Results: ① The survival rate of SAN cells in I/R group [ (51. 79±6. 28)% ] was remarkably significantly lower than in control [ (95. 08±10. 48)% ] (P < 0.001), and very significantly lower than in P + I/R group [ (63. 77±5. 35) % ] (P<0.01), however, those of 5-HD + P + I/R group [(52. 88±6. 25)% ] and 5-HD+I/R group [ (53. 16±5. 35)% ] was significantly lower compared with that in P + I/R group (P <0. 01) ; ② When the average fluorescence intensity of sinoatrial node cells in the control was regarded as 100% , the relative fluorescence intensities of each group were: ( 374±52) % in I/R group, significantly higher than that of control (P <0. 01) ; ( 162±20)% in P + I/R group, declining significantly than that of I/R group (P<0.01); (385?6)% in 5-HD+ P + I/R group and (379±44)% in 5-HD + I/R group, increasing significantly than that of I/R group (P<0.01). Conclusion: ① Simulated ischemia-reperfusion can significantly reduce the survival rate of SAN cells, and can also lead to the overload of intracellular calcium in them.② KATp channel opener, pinacidil, exerts protective effect on the cells under simulated ischemia-reperfusion, which may be associated with the decrease of intracellular calcium loading in them.

钩藤碱抑制麻醉大鼠颈动脉窦压力感受性反射的研究

目的研究钩藤碱(Rhy)对颈动脉窦压力感受性反射(CSB)的作用并探讨其作用机制。方法利用隔离灌流大鼠颈动脉窦技术,确定各项功能参数,如阈压(TP)、饱和压(SP)、平衡压(EP)、工作范围(OR)、最大斜率(PS)和平均动脉压反射性下降幅度(RD)等。Rhy(10、50、100μmol/L)溶于K-H液后灌流窦区,以斜坡方式升降窦内压来观察Rhy对CSB的影响。分别预先灌流一氧化氮合酶抑制剂L-NAME,钾通道阻断剂四乙铵(TEA)和￡-型钙通道开放剂Bay K8644后再给予Rhy,观察它们对Rhy作用的影响。结果Rhy浓度依赖性地抑制了CSB,使其各功能参数改变,TP和SP增大,PS和RD均减小。Rhy的抑制作用不能被L-NAME(300μmol/L)和TEA(1 mmol/L)预处理所取消,而可被Bay K8644(500 nmol/L)明显减弱。结论Rhy抑制了CSB,此作用可能是通过减弱压力感受器的牵张敏感性离子通道的钙内流来实现,而与NO和钾通道无关。