Antioxidant treatment reduces matrix metalloproteinase-2-induced vascular changes in renovascular hypertension
Antioxidant treatment reduces matrix metalloproteinase-2-induced vascular changes in renovascular hypertension
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DOI：
10.1016/j.freeradbiomed.2009.02.011
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发表时间：
2009-05-01
影响因子：
7.4
通讯作者：
Tanus-Santos, Jose E.
中科院分区：
文献类型：
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作者：
Castro, Michele M.;Rizzi, Elen;Tanus-Santos, Jose E.
越来越多的证据表明，与两肾一夹 (2K-1C) 高血压相关的结构和功能性血管变化至少部分是由基质金属蛋白酶 (MMP) 活性的改变引起的。由于活性氧 (ROS) 形成的增加会上调 MMP，因此我们假设抗氧化方法可以减弱 MMP-2 表达/活性的增加以及与 2K-1C 高血压相关的血管功能障碍和重塑。假手术或2K-1C高血压大鼠用tempol 18 mg/kg/天或夹竹桃花青素25 mg/kg/天（或媒介物）治疗。每周监测收缩压。治疗8周后，分离主动脉环以评估内皮依赖性和非依赖性舒张。在苏木精/伊红切片中研究了主动脉壁结构变化的定量形态测量。分别使用二氢乙啶和硫代巴比妥酸反应物质测量主动脉和全身ROS水平。主动脉 MMP-2 水平和活性通过明胶和原位酶谱、荧光测定和免疫组织化学测定。 Tempol 和夹竹桃花青素可减轻 2K-1C 高血压（分别为 181 +/- 20.8 和 192 +/- 17.6 mm Hg，而高血压对照组为 213 +/- 18 mm Hg；均 p0.05），防止 2K-1C 大鼠中发现的血管重塑（所有 p
Mounting evidence indicates that structural and functional vascular changes associated with two-kidney, one-clip (2K-1C) hypertension result, at least in part, from altered activity of matrix metalloproteinases (MMPs). Because MMPs are upregulated by increased formation of reactive oxygen species (ROS), we hypothesized that antioxidant approaches could attenuate the increases in MMP-2 expression/activity and the vascular dysfunction and remodeling associated with 2K-1C hypertension. Sham-operated or 2K-1C hypertensive rats were treated with tempol 18 mg/kg/day or apocyanin 25 mg/kg/day (or vehicle). Systolic blood pressure was monitored weekly. After 8 weeks of treatment, aortic rings were isolated to assess endothelium-dependent and -independent relaxation. Quantitative morphometry of structural changes in the aortic wall was studied in hematoxylin/eosin sections. Aortic and systemic ROS levels were measured using dihydroethidine and thiobarbituric acid-reactive substances, respectively. Aortic MMP-2 levels and activity were determined by gelatin and in situ zymography, fluorimetry, and immunohistochemistry. Tempol and apocyanin attenuated 2K-1C hypertension (181 +/- 20.8 and 192 +/- 17.6 mm Hg, respectively, versus 213 +/- 18 mm Hg in hypertensive controls; both p0.05), prevented the vascular remodeling found in 2K-1C rats (all p