咪达普利对舒张功能不全大鼠心房肌细胞钠通道的影响

Effects of imidapril on sodium current in atrial myocytes in rats with diastolic heart failure

目的:探讨咪达普利对舒张功能不全心衰(DHF)大鼠心房肌细胞钠电流的影响。方法:50只雄性SD大鼠,随机分为对照组、DHF组和低、中、高剂量组,每组10只。腹主动脉缩窄建立DHF模型。低、中、高剂量组大鼠术后灌胃予咪达普利1.5、3、6mg/(kg·d)。4周后心脏超声检测心功能,全细胞膜片钳技术记录通道电流。结果:(1)与对照组比较,DHF组大鼠心脏室间隔(IVS)、左室后壁(LVPW)、左室心脏指数(LVM)和E/A比值增加;咪达普利降低DHF大鼠IVS、PW、LVM和E/A比值,该作用随咪达普利剂量增加而增大;(2)与对照组比较,DHF大鼠心房肌细胞INa峰值电流密度降低,复活延迟;咪达普利增加DHF大鼠心房肌细胞INa峰值电流密度,加快复活,该作用随咪达普利剂量增加而增大。结论:咪达普利增加DHF大鼠心房肌INa峰值电流密度,加快复活,该作用具有剂量依赖性。

Objective To study the effects of imidapril on sodium current in atrial myocytes in rats with diastolic heart failure.Methods 50 SD rats were randomly divided into 5 groups：control group,DHF group,and low-,moderate-,and high-dose groups.DHF model was establised by constriction of the abdominal aorta.The imidapril groups received intragastric administrations of imidapril of 1.5,3,and 6 mg /（kg·d）.After 4 weeks,cardiac function was assessed by echocardiography.Sodium currents were detected using the whole-cell patch-clamp technique.Results As compared with the control group,DHF group exhibited an increase in IVS,PW,LVM and E /A ratio.Imidapril decreased IVS,PW,LVM and E /A ratio in DHF rats in a dose-dependent manner.As compared with the control group,the peak density of atrial INa in DHF group was decreased and time to 50% recovery of INa from inactivation was increased.Imidapril increased the peak density of atrial INa and decreased time to 50% recovery of INa from inactivation in DHF rats.The effects of imidapril on sodium currents were elevated as the increasing dose of the agent.Conclusions Imidapril increases the peak density of atrial INa and decreases time to 50% recovery of INa from inactivation in DHF rats.The effects increase in a dosedependent fashion.