AGING EFFECTS ON CEREBRAL BLOOD VESSELS

衰老对脑血管的影响

• 批准号: 2051534
• 负责人: DONALD D HEISTAD
• 金额: $ 16.17万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2051534
• 关键词: aging; animal old age; antioxidants; arginine; bioassay; blood brain barrier; brain stem; catalase; cerebrovascular disorders; cerebrovascular system; fluorescent dye /probe; free radical oxygen; laboratory rat; microcirculation; muscle relaxation; muscle relaxing factor; nitric oxide; perfusion; pulse pressure wave; spontaneous hypertensive rat; superoxide dismutase; topical drug application; vascular endothelium; vascular smooth muscle; vasoconstrictors; vasodilatation

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.

研究建议检查老化对大脑血液的影响 船舶.目标是研究的机制和后果 衰老过程中内皮依赖性舒张功能受损， 研究大脑血管在衰老过程中的结构变化。 还计划进行研究，以确定是否有功能性变化， 脑血管老化是可逆的。几个假设将是 测试. 首先，研究提出了检查机制的损害， 在体内脑小动脉内皮依赖性舒张。的in 体内生物测定将用于测试释放的假设 内皮源性舒张因子（EDRF）因衰老而受损。两 提出了尝试恢复内皮依赖性 对老年大鼠的正常反应。首先，将应用1-精氨酸 局部至脑小动脉。如果一氧化氮的合成， 基底动脉中的主要EDRF，与缺乏 底物，局部施用1-精氨酸可以改善内皮细胞- 老年大鼠的依赖性反应。其次，抗氧化剂将 管理。对EDRF的反应被氧自由基抑制， 可能在老化过程中产生。计划进行研究，以确定是否 急性给予超氧化物歧化酶（SOD）和过氧化氢酶，或 长期给予PEG SOD，将改善内皮依赖性 在古怪的老鼠身上放松。 第二，研究提出了测试的假设，流量介导的 大脑血管的扩张会因衰老而受损， 缺陷可能使大脑灌注受损。如果答复 受损，计划进行研究，以确定他们是否可以 通过急性或慢性施用抗氧化剂来改善。 第三，脑小动脉中的平滑肌经历萎缩， 衰老计划进行研究以确定脉搏减少是否 压力可能会导致衰老过程中的小动脉萎缩， 小动脉质量的减少足以损害血管收缩剂， 血管舒张反应。 这些学生具有相当大的潜在意义。如果 可以识别内皮依赖性机制的异常， 用1-精氨酸或氧自由基清除剂逆转，它可能是 有可能纠正一个重要的血管老化异常。