波生坦与硝苯地平对脱氧皮质酮-盐敏感高血压鼠主动脉血管重塑的影响  

Effect of bosentan and nifedipine on aortic vascular remodeling in deoxycorticosterone actate-salt hypertensive rats

作　　者：陈建昌[1] 洪小苏[1] 陈亮波[1] 焦阳[1] 徐卫亭[1] 

机构地区：[1]苏州大学附属第二医院心内科,江苏苏州215004

出　　处：《临床心血管病杂志》2006年第5期298-301,共4页Journal of Clinical Cardiology

基　　金：江苏省教育厅自然科学研究基金项目(No:Q2123031)

摘　　要：目的:观察波生坦和硝苯地平对脱氧皮质酮(DOCA)-盐敏感高血压鼠(DHR)血压、主动脉结构、血浆内皮素-1(ET-1)和主动脉组织ET-1 mRNA表达的影响,探讨其可能的作用及其机制。方法:40只SD大鼠, 等分为正常对照组、DHR对照组、波生坦组和硝苯地平组,波生坦组给予波生坦100 mg·kg-1·d-1灌胃,硝苯地平组给予35 mg·kg-1·d-1灌胃,每周测尾动脉血压1次,4周后处死,抽取动脉血放射免疫法测血浆ET-1 浓度,取主动脉分别作病理分析和逆转录聚合酶链反应检测ET-1 mRNA表达。结果:DHR对照组血压明显升高,血管平滑肌细胞肥大,弹力纤维层增厚,中层厚度及中层厚度／内径明显增大。波生坦组血压上升幅度降低, 上述血管组织变化明显改善。硝苯地平可抑制DHR血压上升,血管组织变化与模型对照组相似。血浆ET-1浓度在DHR对照组、波生坦组和硝苯地平组均有显著升高,但以波生坦组升高更为显著;DHR对照组、波生坦组和硝苯地平组主动脉组织ET-1 mRNA表达与正常对照组相比,均有显著增加,但3组间差异无统计学意义。结论:波生坦可降低DHR上升的血压,改善主动脉重塑可能系波生坦阻断了ET-1与其受体结合的结果。硝苯地平能抑制DHR的血压升高,但不能改善主动脉的重塑。Objective：To observe the effect of bosentan and nifedipine on systolic blood pressure（SBP） ,aortic structure, endothelin-1 （ET-1） in plasma and aortic ET-1 mRNA expression of deoxyeorticosterone actate（DOCA）- salt hypertensive rats（DHR）,and to investigate the mechanism. Method： Forty male Sprague Dawley rats were unilaterally nephrectomized and divided into four groups. One group served as normal control group,drinking tap water. In the other three groups,DOCA subcutaneously injection（50 mg·kg^-1·d^-1） and 1% saline drinking water were used to creat hypertensive model. Two of model groups were respectively fed with bosentan （100mg·kg^-1·d^-1 ） and nifedipine（35 mg/kg per day） for 4 weeks, the rest received placebo. The SBP was determined by the tail-cuff method. ET level in plasma was measured by radioimmunoassay. Aortas were dissected,used for his- tologic study. RT-PCR was used to determine the ET-1 mRNA. Result：In model placebo group ,SBP increased significantly. Vascular smooth muscle cells were hypertrophied and proliferated, media thickness（MT） and MT/ lumina diameter（LD） ratio increased significantly. Bosentan could blunt SBP increasing,lessen aortic MT, and alleviated aortic vascular remodeling of DHR. Nifedipine was able to inhibit the development of SBP, but it could not ameliorat vascular remodeling. Plasma ET-1 and ET1 mRNA expressed in model control group, bosentan group and nifedipine group were higher than that in normal control group. The level of ET1 was significantly elevated in bosentan group than that in model control group and nifedipine group. Conclusion： Bosentan could blunt SBP in creasing in DHR, and improve aortic vascular remodeling,which may be the result of its competitive inhibition of endothelin receptors. Nifedipine could inhibit SBP increasing, but had no effect on aortic vascular remodeling in DHR.

关 键 词：抗高血压药 脱氧皮质酮 内皮素 血管重塑 

分 类 号：R98[医药卫生—药品]