NITRIC OXIDE, SUPEROXIDE AND VASCULAR REACTIVITY

描述(改编自《调查者摘要》)：活性氧物种 导致血管功能和条件的变化，如中风， 高血压和动脉粥样硬化。病变的性质和复杂性 动脉粥样硬化的进展表明，这种疾病可能有几种 病因学。自由基的产生与变化有关。 在血管反应性和脂蛋白代谢方面。这些研究 旨在提供有关以下内容的新信息 氧化剂引起的血管壁损伤。需要检验的假设是 高胆固醇血症兔血管功能受损是一种 一氧化氮与超氧阴离子相互作用的后果 自由基，导致产生强有力的氧化剂过氧亚硝酸盐。 在正常的生理条件下会产生活性氧物种， 开发了天然的抗氧化剂清道夫途径，使 氧化剂介导的损伤。在抗氧化防御机制的失衡和 然后，细胞代谢过程的变化有助于发育 动脉粥样硬化性疾病的进展。这篇文章中概述的研究 旨在提供描述蜂窝网络的新信息 参与这些自由基反应的机制，即，自由基 高胆固醇血症兔血管损伤与 黄嘌呤氧化酶在糖胺多聚糖上的结合和浓缩 内皮细胞的表面和血管系统的间质中。 在这项提议中要检验的假设是糖胺多糖- 结合黄嘌呤氧化酶是超氧阴离子自由基的重要来源 因此，过氧亚硝酸盐，并有助于氧化成分 高胆固醇血症。糖胺聚糖的功能或表达可能是 因高脂血症而改变，从而促进合并 血管壁中的脂蛋白以及作为黄嘌呤的位置 酶的结合和结合。分子相互作用中的这些变化 可以影响血管功能的变化，并在血管中发挥重要作用 与高胆固醇血症相关的病理事件。

DESCRIPTION (Adapted from Investigator's Abstract): Reactive oxygen species induced changes in vascular function and conditions such as stroke, hypertension, and atherosclerosis. The nature and complexity of lesion development in atherosclerosis suggests that this disease may have several etiologies. The generation of free radicals is associated with alterations in both vascular reactivity and lipoprotein metabolism. The studies proposed in this application are designed to provide new information about oxidant-induced damage in the vessel wall. The hypothesis to be tested is that impaired blood vessel function in hypercholesterolemic rabbits is a consequence of the interaction between nitric oxide and superoxide anion radical, leading to the production of the potent oxidant peroxynitrite. Reactive oxygen species are generated under normal physiologic conditions, with native antioxidant scavenger pathways developed to minimize oxidant-mediated injury. In imbalance in antioxidant defense mechanisms and changes in cellular metabolic processes then contribute to the development and progression of atherosclerotic disease. The studies outlined in this proposal are designed to provide new information describing the cellular mechanisms involved in these free radical reactions, viz., that free radical injury in blood vessels of hypercholesterolemic rabbits is linked to the binding and concentration of xanthine oxidase at glycosaminoglycan sites on the surface of endothelial cells and in the interstitium of the vasculature. The hypothesis to be tested in this proposal is that glycosaminoglycan- bound xanthine oxidase is an important source of superoxide anion radical and, thus, peroxynitrite, and contributes to the oxidative component of hypercholesterolemia. Glycosaminoglycan function or expression may be altered by hyperlipidemia, thereby facilitating incorporation of lipoproteins in the vessel wall as well as serving as a site for xanthine oxidase binding and incorporation. These changes in molecular interactions can influence changes in vascular function and play an important role in the pathologic events associated with hypercholesterolemia.