埃他卡林等三种结构类型的钾通道开放剂对非血管平滑肌舒张作用的选择性

目的: 研究新结构类型的ATP-敏感性钾通道(K_ATP)开放剂(KCO)、抗高血压新药埃他卡林(iptakalim, Ipt)对胃、回肠和膀胱等非血管平滑肌舒张作用的影响, 并比较Ipt 与其结构完全不同的KCO 、氰胍类的吡那地尔(pinacidil, Pin)和苯并噻二嗪类的二氮嗪(diazoxide, Dia)舒张作用的差异, 为进一步明确Ipt 舒张作用的选择性特征提供一定的依据。方法: 采用大鼠离体胃底、回肠和膀胱肌条3种组织, 以10^-5 mol·L^-1乙酰胆碱预收缩, 观察不同浓度的药物对它们的舒张作用。结果: Ipt 在10^-8 ~10-4mol·L^-1范围内对3 种组织均无显著的舒张作用;Pin 在10^-8 ~ 10^-4 mol·L^-1 范围内对胃底条和膀胱平滑肌等均无显著的舒张作用, 但在10^-5和10^-4mol·L-1时对回肠的舒张率分为28.8 %和51.9 %,诱发显著的舒张作用;Dia 对3 种组织的作用与Ipt相似, 均不引起明显的舒张作用。结论: Ipt 不影响胃、回肠和膀胱的舒张作用, 选择性优于Pin, 与Dia相似;化学结构类型不同的KCO 对回肠、胃和膀胱的作用既相似也有不同。

Relaxation selectivity of three structurally diverse ATP-sensitive potassium channel openers,iptakalim, pinacidil and diazoxide on non-vascular smooth muscles

AIM: To investigate the relaxation effects of iptakalim (Ipt), a novel structural ATP-sensitive potassium channel opener (KCO), compare the relaxation characteristics of Ipt to the other structurally diverse KCOs, pinacidil (Pin)and diazoxide (Dia), and further understand the relaxation selectivity of Ipt. METHODS: Strips of stomach, ileum, and bladder isolated from rats were prepared and treated with different concentrations of drugs after contraction of 10^-5 mol·L^-1 acetylcholine. RESULTS: Ipt at the concentrations of 10^-8-10^-4 mol·L^-1 caused no relaxation effects on strips of stomach, ileum and bladder. The same results as Ipt were detected in diazoxide-treated tissue strips. Pin showed no effects on strips of stomach and bladder, however, Pin at concentrations of 10^-5 and 10-4mol·L^-1 induced significant relaxations in ileum strips compared with the former concentration, and the relaxation rates were 28.8 % and 51.9 %, respectively. CONCLUSION: Ipt shows no effect on the relaxation of stomach, ileum and bladder, which is different from Pin, but the same as Dia. Moreover, similarities and differences in relaxation are also found among the structurally diverse KCOs.