SHR高血压进程中不同类型血管内皮功能损伤及药物修复研究

目的探讨SHR大鼠在高血压发展进程中,不同血管内皮功能损伤程度及抗高血压药物对其的修复。方法以SHR为模型,7～24wk(wk:周龄)给予卡托普利(3.375g.kg-1.d-1),停药观察至32wk。6、18、24和32wk时分别进行病理学切片检查胸主动脉、肠系膜上动脉和心尖小动脉形态结构,及胸主动脉和肠系膜上动脉乙酰胆碱(ACh)浓度依赖性血管舒张功能检测(n=6)。结果SHR在18wk时胸主动脉、肠系膜上动脉和小动脉均出现结构病变,并随时间逐渐加重,三级动脉中胸主动脉病变较之严重,表现为内皮细胞脱落和中膜增厚;随年龄增大SHR胸主动脉和肠系膜上动脉ACh依赖性舒张度均下降,但胸主动脉舒张度降低幅度大于肠系膜上动脉(P=0.10,18wk;P<0.01,24、32wk);卡托普利能抑制18wkSHR胸主动脉舒张度的降低(P<0.05vsSHR),但对肠系膜上动脉没有该作用。结论伴随SHR高血压的发病进程,体内各级动脉内皮细胞均发生损伤,内皮依赖性舒张功能降低,大动脉内皮功能损伤出现早,程度也往往高于中、小动脉,抗高血压药物可抑制大动脉内皮功能障碍,但对中、小动脉内皮功能损伤无作用。

Study in the damage of endothelial function and administration recovery among different arteries during the developing progress of SHR

Aim To evaluate the endothelial dysfunction level of different arteries at different stages of SHR,and the recovery after administration.Methods SHR model was used,captopril(3.375 g·kg~(-1)·d~(-1)) was administered from week 7 to week 24 and the effects were observed continuously until 8 weeks post treatment.Pathological changes of aorta,mesenteric and apex cordis arteries were examined at the time points of 6,18,24,32 wk,and the endothelial-dependent relaxation of the former two preparations were tested by acetylcholine(ACh)(n=6).Results There were pathological changes in the thoracic aorta,mesenteric artery and arteriole at 18 wk,and aggravated along the age.The thoracic aorta demonstrated the most severe pathological changes appearing endothelial cells ablated and tunica media thickening.The significant decline of endothelium-dependent relaxation in aorta,and mesenteric arteries of SHR reflected an aging dependent change of vascular function with the most severe situation in the aorta(P=0.10,18 wk,P<0.01 24,32 wk);captopril increased the aorta vasodilatation of SHR at 18 wk time point,without the effect in mesenteric artery(P<0.05 vs SHR).Conclusions During the progress of SHR,endothelial damages have been observed in all three kinds of vasculatures together with the reduced endothelial-dependent relaxation.The aorta presents earlier and deeper damage than middle and small size vessels,and is sensitive towards the antihypertensive therapy such as the angiotensin converting enzyme inhibitor.