AGING EFFECTS ON CEREBRAL BLOOD VESSELS

有人建议研究衰老对大脑血液的影响。 船只。我们的目标是检查以下机制和后果 衰老过程中内皮依赖的松弛功能受损， 检查衰老过程中脑血管的结构变化。 还计划进行研究，以确定脑功能是否发生变化 衰老过程中的脑血管是可逆的。几个假设将是 测试过。 首先，建议进行研究，以考察脑损伤的机制。 在体脑小动脉内皮依赖性的松弛。An In 体内生物测定将被用来检验释放的假设 内皮源性松弛因子(EDRF)随着年龄的增长而受损。二 提出了尝试恢复内皮依赖性的方法 老年大鼠对正常的反应。首先，将应用1-精氨酸 局部注射到脑小动脉。如果合成一氧化氮，那就是 基底动脉中的一个主要的EDRF，与缺乏 底物，局部应用1-精氨酸可能会改善内皮- 老年大鼠的依赖反应。第二，抗氧化剂将 管理。对EDRF的反应被氧自由基抑制，氧自由基 可能在老化过程中产生。计划进行研究，以确定 急性服用超氧化物歧化酶(SOD)和过氧化氢酶，或 长期服用聚乙二醇超氧化物歧化酶，将改善内皮依赖性 在奇怪的大鼠身上松弛。 其次，有人提出研究来检验流动中介的假说 脑血管的扩张会因年龄的增长而受损，这就是 缺陷可能导致大脑的血流灌注受损。如果响应 是受损的，计划进行研究以确定它们是否可以 通过急性或长期服用抗氧化剂而改善。 第三，脑小动脉中的平滑肌会在 衰老。计划进行研究以确定脉搏的减少 压力可能导致衰老过程中的小动脉萎缩，以及 小动脉质量的减少足以损害血管收缩和 血管扩张剂反应。 这些学生具有相当大的潜在意义。如果 内皮依赖机制的异常可以被识别出来，并且 用1-精氨酸或氧自由基清除剂逆转，可能是 有可能纠正一种重要的血管衰老异常。

Studies are proposed to examine effects of aging on cerebral blood vessels. The goals are to examine mechanisms and consequences of impairment of endothelium-dependent relaxation during aging, and to examine structural changes in cerebral blood vessels during aging. Studies are also planned to determine whether functional changes of cerebral vessels during aging are reversible. Several hypotheses will be tested. First, studies are proposed to examine mechanisms of impairment of endothelium-dependent relaxation in cerebral arterioles in vivo. An in vivo bioassay will be used to test the hypothesis that release of endothelium-derived relaxing factor (EDRF) is impaired by aging. Two approaches are proposed to attempt to restore endothelium-dependent responses to normal in old rats. First, 1-arginine will be applied topically to cerebral arterioles. If synthesis of nitric oxide, which is a major EDRF in the basilar artery, is related to a deficiency of substrate, topical administration of 1-arginine may improve endothelium- dependent responses in aged rats. Second, antioxidants will be administered. Responses to EDRF are inhibited by oxygen radicals, which may be generated during aging. Studies are planned to determine whether acute administration of superoxide dismutase (SOD) and catalase, or chronic administration of PEG SOD, will improve endothelium-dependent relaxation in odd rats. Second, studies are proposed to test the hypothesis that flow-mediated dilatation of cerebral blood vessels is impaired by aging, and that is defect may predispose impaired perfusion of the cerebrum. If responses are impaired, studies are planned to determine whether they can be improved by acute or chronic administration of antioxidants. Third, smooth muscle in cerebral arterioles undergoes atrophy during aging. Studies are planned to determine whether reduction in pulse pressure may contribute to arteriolar atrophy during aging, and whether reduction of arteriolar mass is sufficient to impair vasoconstrictor and vasodilator responses. The students have considerable potential significance. If the abnormality in endothelium-dependent mechanisms can be identified, and reversed with 1-arginine or scavengers of oxygen radicals, it may be possible to correct an important vascular abnormality of aging.