盐酸埃他卡林选择性降压作用的研究

Study on selective antihypertensive effects of iptakalim hydrochloride

目的 :在清醒正常血压犬和“两肾一夹”肾性高血压犬 (RHD)上 ,观察不同剂量盐酸埃他卡林(iptakalimhydrochloride,Ipt)的降压作用特征 ;在清醒正常血压的Wistar大鼠和脑卒中易感型自发性高血压大鼠 (stroke pronespontaneouslyhypertensiverat,SHRsp)上 ,采用无创心功能监测方法 ,观察Ipt对心功能和血流动力学的作用特征 ,以判断其降压作用和对心功能及血流动力学的影响是否具有选择性。方法 :给清醒正常血压犬和RHD口服不同剂量的Ipt,用听诊法测量移于皮鞘内的颈总动脉血压 ,用触诊法测量心率 ,同时记录Ⅱ导联心电图。给清醒正常血压大鼠和SHRsp静脉注射相同剂量的Ipt,采用清醒无创心功能血流动力学实验方法 ,观察Ipt对对心功能和血流动力学的影响。结果 :在RHD模型上 ,单次口服Ipt0 .1 2 5、0 .2 5、0 .5、1 .0mg·kg- 1 后 ,产生剂量依赖性的降压作用 ,0 .5h开始起效 ,2～ 3h达效应峰值 ,其最大降低SBP幅度分别为 1 3、2 3、2 5、3 6mmHg,降压作用维持时间分别为 4、6、6、1 2h。在清醒正常血压犬上 ,单次口服Ipt 0 .8,3 .2 ,1 2 .8mg·kg- 1 ,其中剂量为 0 .8和 3 .2mg·kg- 1 时 ,血压和心率均无明显变化 ,剂量增至 1 2 .8mg·kg- 1 时 ,在给药后 5h之内可以显著降低收缩压和舒张压 。

AIM: To study the antihypertensive effects of iptakalim hydrochloride (Ipt) on conscious 'two kidney one clip' renal hypertensive dogs(RHD), normotensive dogs,conscious normotensive rats (NTR), and stroke prone spontaneously hypertensive rats(SHRsp). METHODS: Conscious RHD were treated with Ipt 0.125 , 0.25 , 0.5 and 1.0 mg·kg -1 , po. Conscious normotensive dogs were treated with Ipt 0.8 , 3.2 and 12.8 mg·kg -1 , po. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rates (HR) were investigated before and after administration. The conscious noninvasive cardiac functions and hemodynamics method was used to determine the effects of Ipt ( 0.5 mg·kg -1 , iv) on heart rate, systolic, diastolic and pump functions in NTR and SHRsp. RESULTS: Ipt at the doses of 0.125 , 0.25 , 0.5 and 1.0 mg·kg -1 decreased the blood pressure in a dose dependent manner in RHD. The maximal △SBP were 13, 23, 25 and 36 mmHg, respectively. The lasting time of hypotensive effects was 4, 6, 6 and 12 hours, respectively. In consciously normotensive dogs, Ipt at the doses of 0.8 and 3.2 mg·kg -1 had no effects on blood pressure and heart rates. When the dose increased to 12.8 mg·kg -1 , Ipt could decrease SBP and DBP significantly during 5 hours after administration. The maximal △SBP was 26 mmHg. Ipt had no effects on HR. The dose was 25.6 times as much as that in RHD. HR, ventricular contractile function and cardiac output were decreased significantly, left ventricular ejection time (LVET) and left ventricular diastolic time (ZO) were prolonged by Ipt at the dose of 0.5 mg·kg -1 in SHRsp, iv. Under the same experimental conditions, those parameters remained to be unchanged in NTR. CONCLUSION: Ipt has selectively antihypertensive effects. Ipt also has selective effects on cardiac functions and hemodynamics in SHRsp. It suggests that Ipt has significant effect on hypertensive animals but little effect on normotensive animals.