TJ0711对自发性高血压和哇巴因-高血压麻醉大鼠的急性降压

目的:观察新型肾上腺素α,β受体双重阻断剂TJ0711静脉注射对自发性高血压大鼠(SHR)和哇巴因-高血压大鼠(OHR)2种模型的急性降压作用。方法:制备OHR模型:SD大鼠连续8周腹腔注射30 μg·kg^-1·d^-1哇巴因,将收缩压>21.3 kPa(1 kPa≈7.5 mmHg)者随机分为生理盐水(N.S)组、TJ0711 0.3,0.9,2.7 mg·kg^-1剂量组、阳性对照卡维地洛1 mg·kg^-1组(n=12);购得的SHR分组方法同OHR。用10%乌拉坦(1.3 g·kg^-1,i.p)麻醉,仰位固定,分离一侧颈总动脉插管连接多通道生理记录仪测血压和心率,颈外静脉插管给药。观察给药前后大鼠收缩压、舒张压、心率的变化,分析TJ0711静注降压作用规律。结果:TJ0711静注给药后2~15 min即达到最大降压水平,降压作用维持25~75 min。对SHR和OHR两种高血压模型收缩压与舒张压下降趋势一致,但对SHR收缩压、舒张压最大降压幅度高于OHR。结论:TJ0711静脉注射能快速、短效降低SHR和OHR两高血压模型大鼠的血压同时使心率适当减慢,具有良好的急性降压特点。

Acute hypotensive effects of TJ0711 on model rats with spontaneous hypertension and Ouabain hypertension

OBJECTIVE To observe hypotensive effects of TJ0711, a novel α, β blocker, in two hypertensive models, spontaneously hypertensive rats (SHR) and Ouabain hypertensive rats (OHR) by intravenous administration.METHODS OHR models were prepared by administering ouabain at 30 μg·kg^-1·d^-1 i.p for 8 weeks to normal SD rats. Then rats with SBP>21.3 kPa (1 kPa≈7.5 mmHg) were randomly divided into NS group, TJ0711 0.3, 0.9, 2.7 mg·kg^-1 groups and carvedilol 1 mg·kg^-1 positive control group (n=12). Purchased SHR were grouped in the same way. Rats anesthetized with 10% urethane (1.3 g·kg^-1, i.p) had intravenous intubation and their unilateral carotid artery was isolated to connect multi-channel physiologic recorder to measure blood pressure and heart rate. Then changes in SBP (systolic blood pressure), DBP (diastolic blood pressure) and HR (heart rate) were observed before and after administration of TJ0711, to analyze the acute hypotensive effects.RESULTS TJ0711 showed maximum hypotensive effects 2-15 min after drug administration and maintained for 25~75 minutes. Intravenous TJ0711 for SHR and OHR showed similar effects. SBP and DBP decreased in the same trend, but hypotensive effect in SHR was stronger than that in OHR, and SBP decreased greater than DBP.CONCLUSION TJ0711 by intravenous route can effectively reduce SBP and DBP of SHR and OHR, and slow heart rate appropriately. TJ0711 shows good acute antihypertensive characteristics of fast and short duration of action.