血管紧张素-(1-7)可改善球囊损伤后血管的舒张功能探讨

Chronic angiotensin-(1-7) administration improves endothelium-dependent vasodilation in rabbits with balloon injury

目的血管损伤可致内皮依赖性血管舒张受损,进而发展为动脉粥样硬化或血管再狭窄。可见,改善血管损伤后的舒张功能可能延缓或减轻再狭窄或动脉硬化的发展。本研究主要观察血管紧张素(angiotensin, ANG)-(1-7)在球囊损伤后对血管舒缩功能的影响,从而了解ANG-(1-7)减轻球囊损伤后再狭窄的可能机制。方法 24只新西兰白兔行腹主动脉球囊损伤术后随机分为对照组、ANG-(1-7)组、ANG-(1-7)+A-779组,每组8只。其中对照组经渗透压微泵给予生理盐水,ANG-(1-7)组和ANG-(1-7)+A-779组分别给予ANG-(1-7)576μg·kg^-1·d^-1或/和其特异性受体拮抗剂A-779 576μg·kg^-1·d^-1,持续4周。并于术前、术后和4周后记录心率、有创血压、腹主动脉血流频谱,4周处死行腹主动脉切片,HE染色。结果球囊损伤术后即刻引起了腹主动脉收缩期峰值流速(peak systolic velocity, PSV)、阻力指数(resistance index, RI)和搏动指数(pulse index, PI)的明显升高(P <0.05)。相反,舒张末期流速(end diastolic velocity, EDV)明显下降(P <0.05)。4周后,PSV,RI和PI较术后即刻有所下降,EDV有所升高,差异有统计学意义(P <0.05)。而平均血流速度(mean velocity,Vmean)在术后即刻即出现明显降低(P <0.05),随着再狭窄的发生,4周后进一步下降(P <0.05)。持续微泵给予ANG-(1-7)可改善再狭窄所致的EDV,RI,PI升高(P <0.05),A-779可部分逆转ANG-(1-7)的作用。结论 ANG-(1-7)可减轻球囊损伤后腹主动脉的舒缩功能,减轻再狭窄程度。

Objective Endothelium-dependent vasodilation is impaired in vascular injury, even before the development of atherosclerosis or restenosis. The purpose of this study was to determine whether angiotensin-(1-7)[ANG-(1-7)] improves vasodilation in rabbits with balloon injury. Methods Twenty-four New Zealand white rabbits underwent angioplasty in abdominal aorta. The animals were divided into three groups, which were control, ANG-(1-7) and ANG-(1-7)+A-779 group. Subsequently, an osmotic minipump was implanted to deliver saline, ANG-(1-7) or A-779 for 4 weeks. Vascular reactivity was measured before, after balloon injury and 4 weeks after drugs delivery. Results All rabbits with vascular injury showed that the peak systolic velocity(PSV), resistance index(RI)and pulse index(PI) of abdominal aorta were significantly increased after balloon dilation(P < 0.05), and decreased 4 weeks after restenosis(P<0.05). In contrast, end diastolic velocity(EDV) was decrease after balloon dilation(P<0.05), and lightly increase 4 weeks later(compared to immediately after balloon injury, P<0.05). The mean velocity(Vmean) declined after balloon injury(P<0.05), and further declined 4 weeks later(P<0.05). Intravenous administration of ANG-(1-7) improved EDV, RI and PI 4 weeks after restenosis. A-779, the antagonist of ANG-(1-7),reduced effects of ANG-(1-7) partially. Conclusion ANG-(1-7) attenuates vascular restenosis and improves endothelium-dependent vasodilation in rabbits with balloon injury.