缬沙坦对卒中易感型自发性高血压大鼠脑血管结构的影响

Effect of valsartan on morphometry of cerebral arteries in stroke prone spontaneously hypertenslve rat

目的 :研究长期口服血管紧张素Ⅱ 1型受体拮抗剂———缬沙坦对卒中易感型自发性高血压大鼠(SHRsp)脑血管形态结构的影响 ,探讨其可能的脑保护机制。 方法 :6周龄雄性SHRsp2 6只随机分为 3组 ,以 8只 6周龄雄性正常血压大鼠 (WKY)作为正常对照 ,记录血压和脑卒中临床表现评分 ,18周后断头处死 ,镜下观察脑血管结构。结果 :① 18周后SHRsp组和小剂量缬沙坦 (2 0mg·kg-1·d-1)用药组 (SHRSP加V2 0 组 )血压均分别高于WKY组和大剂量缬沙坦 (4 0mg·kg-1·d-1)用药组 (SHRSP加V40 组 ) ,P <0 .0 5。②SHRsp组脑卒中临床表现评分明显高于SHRSP加V2 0 组和SHRSP加V40 组 ,SHRSP组死亡率为 33.33% ,SHRSP加V2 0 组和SHRSP加V40 组均无死亡。③SHRsp组脑动脉中膜厚度 /管腔半径的比值明显高于WKY组、SHRSP加V2 0 组和SHRSP加V40 组 ,P<0 .0 5 ;而后三者之间脑动脉中膜厚度 /管腔半径的比值差异均无显著性意义 (P >0 .0 5 )。结论 :缬沙坦可通过降低SHRsp脑动脉中膜厚度 /管腔半径的比值、干预血管重构发挥脑血管保护作用 ,此作用与血压无关。

Objective:To investigate the effects of AT 1 receptor antogonist Valsartan on vascular structure in stroke prone spontaneously hypertensive rat (SHRsp).Methods:Twenty six 6 week aged SHRsp were divided into Valsartan 40 mg·kg -1 ·d -1 group (n=8), Valsartan 20 mg·kg -1 ·d -1 group (n=9) and vehicle group (n=9), and 8 sex and age matched WKY severed as control group (n=8). SHRsp were administered 40 mg·kg -1 ·d -1 Valsartan or 20 mg·kg -1 ·d -1 Valsartan or equal volume of 0.9 % saline solution for 18 weeks by gavage, respectively. The systolic blood pressure was measured by tail cuff sphygmomanometry and clinical score of stroke and survival time of SHRsp were recorded.Results:Oral 40 mg·kg -1 ·d -1 Valsartan delayed the development of severe hypertension and prevented stroke in saline drinking SHRsp. 20 mg·kg -1 ·d -1 Valsartan did not affect on systolic blood pressure but prevented the occurrence of stroke. The clinical scores of stroke and the incidence of stroke by microscope in Valsartan 40 mg·kg -1 ·d -1 group and Valsartan 20 mg·kg -1 ·d -1 group were both decreased than vehicle group (P< 0.05 , respectively). The media to lumen ration in cerebro arteria of SHRsp was higher than WKY (P< 0.05 ). Both 40mg·kg -1 ·d -1 and 20mg·kg -1 ·d -1 Valsartan reduced the media to lumen ration and media cross sectional area of the cerebral arteria in comparison to vehicle group (P< 0.05 , respectively).Conclusion:Chronic AT1 receptor antogonist therapy with Valsartan markedly reduces both hypertension and end organ damage by preventing the development of cerebrovascular lesion on SHRsp in the absence of a blood pressure fall.