盐酸法舒地尔对血管舒缩功能的调节作用

Effects of hydroxyl fasudil on vascular relaxation and contraction activity

目的观察盐酸法舒地尔(hydroxyl fasudil,HF)对犬脑血管痉挛的舒张作用,并采用兔离体胸主动脉环进一步探讨其舒张血管的作用机制。方法经十二指肠给予麦角胺咖啡因片(0.5mg+50mg).kg-1建立犬脑血管痉挛模型,观察给予HF后2h内脑血流量、脑血管阻力、股动脉血流量、股动脉血管阻力、心率、收缩压、舒张压及平均动脉压的变化;用离体血管环实验方法观察HF对血管舒缩作用的影响。结果①犬脑血管痉挛模型中,HF1mg.kg-1给药后脑血管阻力降低,5～120min脑血流量增加;但对心率、收缩压、舒张压及平均动脉压影响较轻微。②离体血管实验中,HF对甲氧明(methoxamine,Met)及氯化钾(postassium,KCl)引发的收缩均有明显的舒张作用,且作用在去内皮与内皮完整的血管标本之间无差异(P>0.05)。结论对犬痉挛脑血管HF静脉给药可明显扩张脑血管,降低脑血管阻力,增加脑血流量,对外周股动脉血管亦有扩张作用,但作用较弱。HF的舒血管作用与血管内皮细胞无明显相关,此作用为非内皮依赖性舒张作用。

Aim To investigate direct effect of hydroxyl fasudil （HF） on cerebrovascular spasm of dogs and to explore mechanisms of its action in rabbit aortic strips. Methods Cerebrovascular spasm （CVS） of dogs were obtained by treating cafergot （0. 5 mg ＋50 mg） ·kg^-1 through duodenum, and several parameters were observed two hours later, which included cerebral blood flow （ CBF ）, cerebral vascular resistance （ CVR ）, femoral artery blood flow （FBF）, femoral vascular resistance （ FVR ）, heart rate （ HR ）, systolic blood pressure （SBP）, diastolic blood pressure （DBP） and mean arterial blood pressure （MABP） ; the influence of HF on vascular was measured by applying isolated blood vessel rings method. Results （ 1 ） After being treated with HF （ 1 mg· kg^-1 ）, the CBF of dogs increased during 5 - 120 min and the CVR decreased during 10 -120 min; however, there was not significant effect on HR, SBP, DBP and MABP. （2） HF had negative regulation of the vasocontractivity to Met and KC1 and both these actions had no obvious difference in endothelium-intact and endothelium-removal groups （P 〉 0. 05）. Conclusions HF could not only relax cerebral vessels, reduce the CVR and enhance the CBF, but also dilate the femoral vessels of CVS dogs. Nevertheless, the latter action was much weaker. Furthermore, there was no relationship between effects of HF on vascular relaxation and contraction activity and the blood vessel endothelium.