摘要
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3×10-6,1×10-5,3×10-5,1×10-4mol/L浓度时,对去甲肾上腺素(NE,1×10-6mol/L)诱发大鼠离体胸主动脉环收缩的影响。观察内皮细胞型一氧化氮合酶(eNOS)抑制剂左旋硝基精氨酸甲酯(L-NAME,1×10-4mol/L)、一氧化氮供体L-精氨酸(L-Arg,1×10-5mol/L)、特异性钙非依赖可诱导型(iNOS)抑制剂N-3-氨甲基-苄基-乙酰氨(1400W,1×10-5mol/L)对咪达唑仑作用的影响,以及咪达唑仑对血管环外钙依赖性收缩和内钙依赖性收缩的影响。结果以上浓度的咪达唑仑对NE预收缩的大鼠离体胸主动脉环有舒张作用。用L-NAME、L-NAME合用L-Arg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,差异有统计学意义(P<0.05),L-Arg和1400W对咪达唑仑的舒血管作用没有影响(P>0.05)。1×10-4mol/L的咪达唑仑可明显抑制血管环外钙依赖性收缩和内钙依赖性收缩(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,其舒张反应可能与内皮产生的一氧化氮有关,通过抑制外钙内流和内钙释放发挥舒张作用。
Objective To study the effects of midazolam on isolated thoracic aorta rings of rats and the mechanism by which it works.Methods The ex-vivo vascular tone test was used to observe the effects of midazolam（3×10-6 mol/L,1×10-5 mol/L,3×10-5 mol/L and 1×10-4 mol/L） on norepinphrine-contracted（NE,1×10-6 mol/L） isolated thoracic aorta rings of rats.The effects of NOS inhibitor L-NAME（1×10-4 mol/L）,NO precursor L-Arg（1×10-5 mol/L）,specific NOS inhibitor 1400W（1×10-5 mol/L） on midazolam,and effect of midazolam on the extracellular Ca2＋-dependent contraction and intracellular Ca2＋-dependent contractions were studied.Results At the above mentioned concentrations,midazolam was shown to dilate the isolated thoracic aortic rings of rats.Compared with no pre-contraction,effects of midazolam on thoracic aortic rings were statistically different with pre-contraction using L-NAME alone or in combination with L-Arg（P0.05）,but not with pre-contraction using L-Arg（P0.05） or 1400W（P0.05）.Midazolam at 1×10-4 mol/L significantly inhibited the extracellular and intracellular Ca2＋-dependent contraction.Conclusion Midazolam may produce a remarkable concentration-dependent vasodilatation on aorta rings of adult rats.The mechanism of this action may be related to endothelial NO but not to NO donors,and may involve inhibition of extracellular and intracellular Ca2＋-dependent contractions.
出处
《中国药物与临床》
CAS
2011年第3期289-291,共3页
Chinese Remedies & Clinics
