咪达唑仑对大鼠离体胸主动脉环的舒张机制研究

Effects of Midazolam on Isolated Thoracic Aortic Rings of Rats

目的观察咪达唑仑对大鼠离体胸主动脉环张力的影响,并探讨其作用机制。方法采用离体血管张力试验方法。观察咪达唑仑在3×10-6mol/L、1×10-5mol/L、3×10-5mol/L、1×10-4mol/L浓度时,对去甲肾上腺素(NE,1×10-6mol/L)、氯化钾(KCl,60 mmol/L)诱发大鼠离体胸主动脉环收缩的影响。观察Na+/Ca2+交换体阻断剂KB-R7943(1×10-6mol/L)、KV通道阻断剂4-AP(4-AP,1×10-3mol/L)、KATP通道阻断剂格列苯脲(Gli,1×10-5mol/L)、KCa通道阻断剂四乙胺(TEA,1×10-2mol/L)、KiR通道阻断剂氯化钡(BaCl2,1×10-3mol/L)对咪达唑仑作用的影响。结果各浓度咪达唑仑对预收缩的大鼠离体胸主动脉环有舒张作用。用KB-R7943、4-AP、TEA及BaCl2预处理的血管环对咪达唑仑的舒张反应与未经处理时比较无统计学意义(P>0.05)。Gli可减弱咪达唑仑对血管环的舒张作用(P<0.05)。结论咪达唑仑对大鼠胸主动脉环具有浓度依赖性的舒张作用,其舒张反应与Na+/Ca2+交换体、KV通道、KCa通道和KiR通道无关,可能与KATP通道有关。

Objective To investigate the effects of midazolam on isolated thoracic aorta rings pre-contracted by norepinphrine（NE） or potassium chloride（KCl） in rats.Methods Rings of the isolated rat thoracic aorta were mounted in organ baths.The isometric contractile force was measured.The effects of midazolam（at the concentration of 3×10-6 mol/L,1×10-5 mol/L,3×10-5 mol/L,and 1×10-4 mol/L） on isolated thoracic aorta rings pre-contracted by norepinphrine（NE,1×10-6 mol/L） or potassium chloride（KCl,60 mmol/L） were observed.The vasorelaxing action of midazolam and effects of various drugs which include KB-R7943（1×10-6 mol/L）,tetraethtylamine（TEA,1×10-2 mol/L）,barium chloride（BaCl2,1×10-3 mol/L）,glibenclamide（Gli,1×10-5 mol/L） and 4-aminopyridine（4-AP,1×10-3 mol/L） were observed in the rings.Results Midazolam concentration-dependently reduced the contraction of isolated thoracic aortic rings pre-contracted in rats.The contraction could be prevented by pretreatment with the K＋ channel inhibitors Gli（P0.05）.KB-R7943,TEA,BaCl2 and 4-AP could not inhibit vasorelaxant effects of midazolam（P0.05）.Conclusion Midazolam could produce remarkable vasodilatation on NE or KCl pre-contracted aorta rings in adult rats.KATP channel might play an important role in the relaxation of the isolated thoracic aortic rings pre-contracted of rats.