Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen
Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen
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DOI：
10.1152/ajpheart.00079.2002
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发表时间：
2002-10-01
影响因子：
4.8
通讯作者：
Faraci, FM
中科院分区：
文献类型：
--
作者：
Didion, SP;Ryan, MJ;Faraci, FM
本研究考察了长期表达人肾素（R+）和人血管紧张素原（A+）的小鼠的血管功能和超氧化物的作用。研究了R+/A+小鼠及其正常血压的同窝小鼠（RA-小鼠）的主动脉反应。R+/A+小鼠血管对乙酰胆碱的内皮依赖性松弛受到损害（R+/A+和RA-小鼠对100 μ m乙酰胆碱的最大松弛分别为45 +/- 5%和65 +/- 3%，P < 0.05）。R+/A+小鼠血管内皮非依赖性扩张剂、一氧化氮和硝普苷的松弛也受到损害。在R+/A+和RA-小鼠中，对内皮不依赖的非一氧化氮扩张剂罂粟碱的最大血管松弛作用相似。R+/A+小鼠血管与铁（1mm）孵育，铁是一种超氧化物清除剂，可改善对乙酰胆碱、一氧化氮和硝普苷的松弛。相比之下，用含铜sod抑制剂二乙基二硫代氨基甲酸酯（1mm）孵育后，R+/A+和RA-小鼠的乙酰胆碱和硝普苷诱导的血管舒张均有所减少。利用荧光素增强化学发光（5 μ M荧光素）和氢乙胺基荧光共聚焦显微镜测量，R+/A+小鼠血管中的基础超氧化物水平较高，并且对铁和聚乙二醇- sod敏感。这些结果表明，在慢性血管紧张素ii依赖性高血压的遗传模型中，增加的超氧化物有助于一氧化氮介导的松弛受损。
This study examined vascular function and the role of superoxide in mice that chronically express human renin (R+) and human angiotensinogen (A+). Responses of aortas from R+/A+ mice and from their normotensive littermates (RA- mice) were examined in vitro. Endothelium-dependent relaxation to acetylcholine was impaired in vessels from R+/A+ mice (e. g., maximal relaxation to 100 muM acetylcholine was 45 +/- 5% and 65 +/- 3% in R+/A+ and RA- mice, respectively; P < 0.05). Relaxation was also impaired to the endothelium-independent dilators authentic nitric oxide and nitroprusside in vessels from R+/A+ mice. Maximal vasorelaxation to the endothelium-independent, non-nitric oxide dilator papaverine was similar in R+/A+ and RA- mice. Incubation of vessels from R+/A+ mice with Tiron (1 mM), a superoxide scavenger, improved relaxation to acetylcholine, nitric oxide, and nitroprusside. In contrast, incubation with diethyldithiocarbamate (1 mM), an inhibitor of copper-containing SODs, reduced acetylcholine- and nitroprusside-induced relaxation in vessels from both R+/A+ and RA- mice. Basal superoxide levels, measured with lucigenin-enhanced chemiluminescence (5 mu M lucigenin) and hydroethidine-based fluorescent confocal microscopy, were higher in vessels from R+/A+ mice and were Tiron and polyethylene glycol-SOD sensitive. These results suggest that increased superoxide contributes to impaired nitric oxide-mediated relaxation in this genetic model of chronic angiotensin II-dependent hypertension.