咪达唑仑对离体猪冠脉环舒张功能的影响及其机制研究

Vasodilatory effect of midazolam on pre-contractions of in-vitro porcine coronary artery and its mechanisms

目的本实验观察咪达唑仑(midazolam)对离体猪冠状动脉环的作用,并探讨其作用机制。方法采用离体血管张力测定实验方法,记录咪达唑仑对KCl(30 mmol·L^(-1))预收缩猪冠状动脉环张力的变化及不同工具药的影响。结果各浓度组咪达唑仑(3×10^(-6)~1×10^(-4)mol·L^(-1))对预收缩猪冠脉环产生浓度依赖性舒张作用,内皮完整组舒张作用强于去内皮组(P<0.05);在KCl预收缩基础上,加入NOS抑制剂L-NAME、L-NAME+L-Arg后,咪达唑仑舒血管作用明显减弱(P<0.05),而加入外源性的NO合成底物L-Arg、i NOS抑制剂1400W、环氧合酶抑制剂Indo均不能抑制咪达唑仑的舒血管作用;Na^+/Ca^(2+)交换体特异性阻断剂KBR7943亦不能抑制咪达唑仑的舒血管作用;钾通道阻断剂K_(ATP)阻断剂Gli可以抑制咪达唑仑的舒张冠脉作用(P<0.05),BKCa阻断剂TEA、Kir阻断剂Ba Cl2、KV阻断剂4-AP则不能改变咪达唑仑的舒张冠脉作用。结论咪达唑仑可浓度和内皮依赖性地舒张KCl预收缩的猪冠脉环,内皮分泌的NO参与了其舒血管作用,外源性NO、i NOS以及PGI2的合成与其舒血管作用无关,咪达唑仑对猪冠脉的舒张可能与K_(ATP)通道有关,与Na^+/Ca^(2+)交换体、K_V通道、BK_(Ca)通道、K_(ir)通道无关。

Aim To investigate the effects of midazolam on porcine isolated coronary artery rings pre-contracted by potassium chloride（ KCl） and the possible mechanism. Methods The vessel tension recorder system was used. Isotonic tension of porcine isolated coronary artery rings precontracted by KCl（ 30 mmol·L-1） was recorded. The vasorelaxing action of midazolam and effects of various drugs were observed in the rings. Results Midazolam（ 3 × 10（-6） 1 × 10（-4）mol·L-1） respectively concentration-dependently reduced the contraction induced by KCl,and there was significant difference between the rings with intact and denude endothelium（ P〈0. 05）. On KCl-induced precontraction,midazolam＇s relaxation was depressed by LNAME and the blend of L-NAME and L-Arg（ P〈0. 05）, but was not affected by Indo,L-Arg and1400 W. The contraction was not prevented by pretreatment with the inhibitor of Na＋/Ca2＋exchanger（ KBR7943）. The inhibitor of K（ATP）（ Gli） restrained the diastolic function of midazolam（ P〈0. 05）,while the inhibitor of BKCa（ TEA）,Kir（ Ba Cl2）,KV（ 4-AP） had no obvious effect. Conclusions Midazolam produces remarkable vasodilatation on KCl pre-contracted porcine isolated coronary artery rings. Its relaxtion effect is via concentration-dependent and endothelium-dependent mechanisms and relevant to the production of NO. Na＋/Ca2＋exchanger is not involved midazolam＇s vasodilatation on KCl pre-contracted porcine coronary artery rings. The relaxant mechanism of midazolam may be concerned with K（ATP）. The K（ir）,BK（Ca） and KV may be not involved.