NITRIC OXIDE, SUPEROXIDE AND VASCULAR REACTIVITY

描述（改编自研究者摘要）：活性氧 引起的血管功能和疾病如中风的变化， 高血压和动脉粥样硬化。 病变的性质和复杂性 动脉粥样硬化的发展表明，这种疾病可能有几个 病因学 自由基的产生与 在血管反应性和脂蛋白代谢方面。 研究 本申请中提出的建议旨在提供有关 氧化剂引起的血管壁损伤。 待检验的假设是 高胆固醇血症兔子的血管功能受损是一种 一氧化氮和超氧阴离子之间相互作用的结果 自由基，导致生产的有效氧化剂过氧亚硝酸盐。 活性氧在正常生理条件下产生， 天然抗氧化剂清除途径的开发，以尽量减少 氧化剂介导的损伤 抗氧化防御机制失衡， 细胞代谢过程的变化则有助于发育 和动脉粥样硬化疾病的进展。 本文中概述的研究 建议旨在提供新的信息，描述蜂窝 参与这些自由基反应的机制，即，的自由基 高胆固醇血症家兔血管损伤与 黄嘌呤氧化酶在糖胺聚糖位点的结合和浓度 内皮细胞的表面和脉管系统的内膜中。 本提案中要检验的假设是糖胺聚糖- 结合黄嘌呤氧化酶是超氧阴离子自由基的重要来源 和，因此，过氧亚硝酸盐，并有助于氧化组分的 高胆固醇血症 糖胺聚糖的功能或表达可能与 通过高脂血症改变，从而促进 脂蛋白在血管壁以及作为一个网站的黄嘌呤 氧化酶结合和掺入。 这些分子间相互作用的变化 可以影响血管功能的变化，并在 与高胆固醇血症相关的病理学事件。

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.