【摘要】 目的　探讨 ATP敏感钾通道 (KATP)开放剂 EMD56 431 对清醒自发性高血压大鼠 (SHR)和肾性高血压大鼠(RHR)血压的影响。方法　采用静脉注射和灌胃给药的方式 ,经颈总动脉插管 ,动态监测动脉收缩压 (SAP) ,舒张压(DAP)及心率 (HR)的变化。并测定小鼠灌胃给予 EMD56 431 时的半数致死剂量 (L D50 )。结果　静注或灌胃给予 EMD56 4312 5、 5 0、 10 0 μg/ kg均可使 SHR血压产生剂量依赖性的下降 ,同时反射性加快 HR。前者降压维持时间分别为 4 5 min、6 h和 6 h以上 ,后者可分别维持 4 5 m in、 1h和 6 h以上。静注和灌胃 EMD56 431 产生的效应相当。灌胃 EMD56 431 亦可使RHR血压产生剂量依赖性的下降 ,降压维持时间分别为 30 m in、 4 5 min和 6 h以上。小鼠 L D50 为 8.5 4 mg/ kg,95 %可信区限为 7.87～ 9.93mg/ kg。结论　 EMD56 431 对 SHR和 RHR有显著而持久的降压作用 ,安全有效 ,且该药生物利用度较高 ,具有广阔的临床开发前景更多还原

【Abstract】 Objective To study the effects of a novel potassium channel activator, EMD 56431 on blood pressure in spontaneously hypertensive rat (SHR) and renal hypertensive rat (RHR). Methods The different doses of EMD 56431 were administrated by injection into vein (i.v.) or intragastric irrigation (i.g.), to monitor the changes of systolic blood pressure (SAP), diastolic blood pressure (DAP) and mean arterial pressure (MAP) by cannulation in common carotid artery. The medial lethal dose (LD 50 ) in mice by i.g. EMD 56431 was calculated. Results Administation of EMD 56431 (25, 50, 100 g/kg, i.v. or i.g.) could produce hypotensive effects in a dose dependent manner and reflexly increase heart rates (HR) of SHR. The persisting duration of i.v. EMD 56431 was 45 min, 6 h, and over 6 h, and the duration was 45 min, 1 h, and over 6 h by i.g. EMD 56431 . Both of i.v. and i.g. EMD 56431 had comparable potency. The range of LD 50 was 7.87 to 9.93 mg/kg in mice. Conclusion EMD 56431 can markedly and continuously decrease the blood pressure in RHR and SHR. EMD 56431 is safe and effective and has a high bioavailability.更多还原