血管紧张素-(1-7)对自发性高血压大鼠去外膜颈动脉血管结构和功能的影响

Effect of angiotensin-(1-7) on intimal hyperplasia and blood flow in carotid artery after adventitia removal in spontaneously hypertensive rats

目的:研究血管紧张素-(1-7)[Ang-(1-7)]对自发性高血压大鼠(SHR)一侧颈动脉去外膜血管结构和功能的影响。方法:24只SHR去除右侧颈动脉外膜后,随机分为3组(每组8只):SHR组、Ang-(1-7)组和Ang779[Ang-(1-7)拮抗剂]组;8只WKY鼠作为对照组(WKY组)。去除大鼠右侧颈动脉外膜左侧作假手术对照。颈静脉给药2周,测量尾动脉收缩压(SBP)、双侧颈动脉血流量和血浆及双侧颈动脉血管紧张素Ⅱ(AngⅡ)浓度。取双侧颈动脉制成光镜标本,病理图象分析系统测定颈动脉内膜和中膜增生状况。免疫组织化学方法测定双侧颈动脉血管紧张素1(AT1)受体蛋白表达。TUNEL法检测血管组织细胞凋亡。结果:Ang-(1-7)组SBP较Ang779组和SHR组显著下降(P<0.01)。Ang-(1-7)组未去外膜侧和去外膜侧内膜增生较SHR组和Ang779组明显改善(P<0.01)。Ang-(1-7)组去外膜侧颈动脉血流量显著高于SHR组和Ang779组(P<0.01)。去外膜侧颈动脉AngⅡ浓度显著高于未去外膜侧(P<0.01)。SHR组和Ang779组去外膜侧颈动脉AT1受体蛋白表达显著高于未去外膜侧(P<0.01),Ang-(1-7)组未去外膜侧和去外膜侧颈动脉AT1受体蛋白表达明显低于SHR组和Ang779组(P<0.01)。Ang-(1-7)组未去外膜侧和去外膜侧凋亡指数较SHR组和Ang779组显著升高(P<0.01)结论:Ang-(1-7)能降低SHR的收缩压和血管阻力增加去外膜侧颈动脉血流量,抑制去外膜后颈动脉内膜增生。这一作用可能与Ang-(1-7)下调颈动脉AT1受体,促进血管组织细胞凋亡有关。

AIM： To investigate the effect of angiotensin-（1-7） on intimal hyperplasia and blood flow in carotid artery after adventitia removal in SHR. METHODS： Twenty-four spontaneously hypertensive rats （SHR） with right carotid artery adventitia removed were randomly divided into 3 groups （ n = 8, each） ： Ang-（ 1- 7）, Ang779 and SHR control group. Eight Wistar-Kyoto rats were selected as normal control group （WKY group）. Adventitia in right carotid artery was removed by mechanical and chemical means. Adventitia in left carotid artery was sham-operated. Ang-（ 1-7 ） in saline （ 25 μg·kg^-1·h^-1） was infused intravenously for 14 days. The systolic blood pressure （SBP） was taken. The velocity of carotid artery was detected by electromagnetic rheometer. Plasma and carotid artery angiotensin Ⅱ （Ang Ⅱ ） levels were measured by radioimmunoassay. The intimal hyperplasia was measured by computed video processing. The expression of local angiotensin Ⅱ type 1 receptor （AT1R） protein in both arteries was determined by immunohistochemistry method. The apoptosis of vascular tissue cell in carotid artery was evaluated by terminal deoxynueleotidyl transferase-mediated Dutp nick-end labeling （TUNEL） assay and measured by image analyse system. RESULTS： SBP in Ang-（1-7） group was significantly lower than that in Ang779 and SHR group （all P 〈0.01）. Compared with Ang779 and SHR group, the carotid blood flow in no adventitia removal in Ang-（1-7） group was increased significantly （ P 〈 0.01 ）. Compared with no adventitia removal, the intimal hyperplasia in adventitia removal was exacerbated significantly （P 〈 0.05）, and it was markedly inhibited in Ang-（1-7） group （P 〈0.01）. Carotid artery Ang Ⅱ level in adventitia removal was significantly higher than that in no adventitia removal （P 〈 0.01 ）. Ang-（1-7） had no significantly effect on plasma and local Ang Ⅱ levels （P 〉 0.05）. The expression of ATI R protein in adventitia removal was significantly higher than that in no adventitia removal in SHR and Ang779 group. Compared with Ang779 and SHR group, the expression of AT1 R protein in Ang-（1-7） group was down-regulated significantly （all P 〈 0.01）. Compared with Ang779 and SHR group, apoptotic index in adventitia removal and no adventltia removal in Ang-（1-7） group was increased significantly （all P 〈 0.01 ）. CONCLUSION： Ang-（ 1-7 ） can significantly improve intimal hyperplasia and increase blood flow in carotid artery with adventitia removal in SHR, which may be related to the down-regulation of local AT1R protein.