川芎嗪对肾性高血压犬血流动力学及冠状动脉血管环功能的影响

Effects of ligustrazine on hemodynamics and contractile function of coronary vascular ring in dogs with renal hypertension

目的观察川芎嗪对肾性高血压犬血流动力学及冠状动脉环舒缩功能的影响。方法以直接测压法测定犬在给予川芎嗪(0.2 g/kg小剂量组和0.6 g/kg大剂量组)前及给药后0.5,1,2,4 h共5个时间点的左室内压力峰值(LVSP)、左室内压力最大上升速率(+LV dp/dtmax)、平均动脉压(MAP)、脉压(PP)。以去甲肾上腺素(NE)和氯化钾(KCl)分别灌流模型组犬离体冠状动脉环,测定川芎嗪对犬冠状动脉环半抑制浓度(IC50),观察川芎嗪对NE及KCl致肾性高血压的冠状动脉环收缩的影响。结果给药后1,2 h 2个时间点测定的川芎嗪有较明显的剂量依赖性地降低肾性高血压犬LVSP、+LV dp/dtmax、MAP的作用;抑制NE和KCl引起的离体冠脉收缩,NE及KCl IC50分别为(1.06±0.65)×10-4mol/L和(1.51±0.26)×10-4mol/L。1×10-4和5×10-4mol/L川芎嗪可使NE引起的内源性钙收缩张力由(1.45±0.18)g分别下降至(0.94±0.42)g和(0.63±0.25)g,外源性钙收缩张力由(2.15±0.47)g降至(1.21±0.42)g和(0.89±0.25)g。结论川芎嗪对肾性高血压犬有降压作用,并可抑制NE和KCl引起的冠脉收缩,其作用机制与抑制平滑肌细胞电压依赖性钙通道和受体操纵钙通道介导的外钙内流和内钙释放,降低心肌收缩力进而影响心功能有关。

Objective It is to explore the effects of ligustrazine on hemodynamics and contractile function of coronary vascular ring in renal hypertensive dogs. Methods The direct manometric method was used to determine the left intraventricular pressure peak value （LVSP） , maximum rising rate of left ventricular pressure （ ± LV dp/dtmax ）, mean arterial pressure （MAP） , pulse pressure （PP） in canines before giving ligustrazine 0.2 g/kg or 0.6 g/kg and after 30 min, 1, 2, 4 h respectively. In norepinephrine（NE） - and potassium chloride （KCl）-induced renal hypertension canines, half inhibitory concentration （ICs0） of coronary vascular ring was determined after perfusing ligustrazine into coronary artery rings. In NE - induced renal hypertension canines, the effect of ligustrazine on contractile function of coronary vascular ring was analyzed. Results Ligustrazine could dose-dependently reduced LVSP, ＋ LV dp/dt MAP in renal hypertensive dogs, and could inhibit coronary vasoconstriction induced by NE and KC1, NE and KC1 IC50 were（ 1.06 ± 0.65 ） ×10-4mol/L and（ 1.51 ± 0.26 ） ×10-4mol/L. 1 ×10-4 and 5 ×10-4mol/L ligustrazine could decrease contraction tension of endogenous calcium from （ 1.45 ± 0.18 ） g to （0.94 ± 0.42）g and （0.63 ± 0.25 ）g, decrease contraction tension of exogenous calcium from （2. 15 ± 0.47 ）g to （1.21 ± 0.42） g and （0.89 ± 0.25）g, Conclusion Ligustrazine has an anti-hypertension effect on renal hypertension, and can inhibit the NE and KCl - induced coronary vasoconstriction in dogs, its mechanism may be related with inhibition of extracellular calcium influx and intracellular calcium release in smooth muscle cell mediated by voltage dependent calcium channel and gymnastics longitudinal calcium channel, thus to decreased myocardial contractility and influent heart function.