雌酚酮衍生物EA204对离体兔血管平滑肌的舒张作用

目的探讨雌酚酮衍生物(EA204)对离体兔血管平滑肌的作用及其机制。方法以离体兔主动脉条为标本,观察了EA204对去甲肾上腺素(NE)、氯化钾(KCl)引起的兔主动脉条收缩的影响;对氯化钙(CaCl2)累积收缩量效曲线的影响,并与维拉帕米(Ver)相比较。通过对比格列苯脲(10μmol.L-1)孵育前后EA204对BaCl2、KCl的舒张量效曲线,研究EA204对钾通道的作用。结果EA204(10~3 mmol.L-1)可以剂量依赖性地抑制NE、KCl收缩的兔主动脉条;EA204(10μmol.L-1)或Ver(0.1μmol.L-1)都使CaCl2累积收缩量效曲线呈剂量依赖性右移,但EA204孵育后CaCl2量效曲线最大反应基本不变,而Ver使最大反应降低;加入格列苯脲(10μmol.L-1)孵育后EA204对BaCl2、KCl收缩的主动脉条的舒张量效曲线发生明显变化,EA204的舒张作用被抑制。结论EA204具有舒张离体兔血管平滑肌的作用,其作用机制与其钙通道阻断作用和钾通道开放作用有关。

Relaxing effect of an estrone derivate EA204 on isolated vascular smooth muscle of rabbits

Objective To study the relaxing effect and its mechanism of an estrone derivate EA204 on isolated vascular smooth muscle of rabbits. Methods Preparations of isolated thoracic aorta of rabbits were prepared for study. The effect of EA204 on the preparations pre-contracted with noradrenaline (NE) or KCl was investigated. The influence of EA204 on the cumulative concentration-response curves of CaCl2 was studied and Verapamil (Ver) was used to compare with EA204 as a noncompetitive inhibitor of Ca2+ channels. The effect of EA204 on K+ channels was studied by observing the difference of relaxing concentration-response curves of EA204 on preparations pre-contracted with BaCl2 or KCl before and after incubation with Glibenclamide (10 μmol?L^-1). Results EA204 (10-3 mmol?L^-1) had a concentration-dependent relaxing effect on isolated aorta strips of rabbits pre-contracted with NE or KCl. Both of incubation of EA204 (10 μmol?L^-1) and Verapamil (0.1μmol?L^-1) shifted the concentration-response curves of CaCl2 to the right, and the rightward shift of the concentration-response curves of CaCl2 were dose dependent. After incubation with Verapamil, the maximum responses of the cumulative concentration-response curves of CaCl2 were significantly decreased. However, the maximum responses were not affected after incubation with EA204. The relaxing concentration-response curves of EA204 on preparations pre-contracted with BaCl2 or KCl before and after incubation with Glibenclamide were significantly changed. Conclusion EA204 can relax isolated vascular smooth muscle of rabbits; the mechanism is associated with the inhibition of Ca ²⁺ channels and the opening of K⁺ channels.