Vascular Function in SOD2-deficient Mice

描述（由申请人提供）：本提案的主要目标是 表征S 0 D2 +/-小鼠中的血管收缩功能。研究计划在 野生型对照和SOD 2 +/-小鼠的动脉和颈动脉， 诸如高血压和动脉粥样硬化之类的疾病，影响这些血管， 是中风的危险因素，并与高水平的反应性 血管壁中的氧物种。在正常情况下， 在体外使用甲萘醌实验性诱导氧化应激， 体内脂多糖，来自野生型对照和SOD 2 +/-小鼠的血管 将被研究以确定血管对乙酰胆碱的反应， 罂粟碱在一些实验中，使用DETCA将抑制SOD 1&3， 进一步揭示了SOD 2的功能。任何观察到的超氧化物依赖性 血管功能障碍将通过使用Tiron抑制超氧化物来确定。 此外，超氧化物和其他活性氧的水平和位置 将在来自野生型对照和SOD 2 + I小鼠的血管中确定种属 在正常条件下和实验诱导氧化应激后。 超氧化物的水平将使用光泽精化学发光和 超氧化物将使用氢乙定染色定位。的位置和 其他活性氧物质（ROS）的相对水平将使用 二氯荧光素（DCF）荧光。

DESCRIPTION (provided by the applicant): The major goal of this proposal is to characterize vasomotor function in SOD2+/-mice. Studies are planned in the aortae and carotid arteries of wild-type control and SOD2+/- mice because diseases such as hypertension and atherosclerosis, which affect these vessels, are risk factors for stroke and are associated with elevated levels of reactive oxygen species in the vascular wall. Under normal conditions, and after experimentally inducing oxidant stress using menadione in vitro and lipopolysaccharide in vivo, vessels from both wild-type control and SOD2+/-mice will be studied to determine vascular responses to acetylcholine and papaverine. In some experiments, SOD1&3 will be inhibited using DETCA to further unmask the function of SOD2. The superoxide dependency of any observed vascular dysfunction will be determined by using tiron to scavenge superoxide. In addition, the levels and location of superoxide and other reactive oxygen species will be determined in vessels from both wild-type control and SOD2+I-mice under normal conditions and after experimentally inducing oxidant stress. Levels of superoxide will be measured using lucigenin chemiluminescence and superoxide will be localized using hydroethidine staining. The location and relative levels of other reactive oxygen species (ROS) will be estimated using dichlorofluorescin (DCF) fluorescence.