Exercise, muscle nutritive blood flow and eNOS in aging

衰老过程中的运动、肌肉营养性血流和 eNOS

• 批准号: 6544416
• 负责人: ROBERT C HICKNER
• 金额: $ 20.93万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6544416
• 关键词: aging; biopsy; blood pressure; cardiovascular disorder prevention; cardiovascular disorder risk; clinical research; electrocardiography; endothelin; enzyme linked immunosorbent assay; exercise; glucose transport; human subject; hypertension; immunocytochemistry; lipolysis; microdialysis; muscle metabolism; muscle tone; nitric oxide synthase; perfusion; prostacyclins; sarcopenia; striated muscles; vasodilation

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of death in the United States, with the incidence of cardiovascular disease increasing rapidly after 60 years of age. A primary risk factor for cardiovascular disease is hypertension, which also increases in prevalence in older individuals. Nitric oxide (NO) induced vasodilatation is reduced with age, resulting in increased blood pressure and reduced limb blood flow, particularly in light of the increased muscle sympathetic tone in older individuals. Impaired production of NO is also associated with peripheral vascular disease, insulin resistance, and Type 2 diabetes. However, there is some evidence that exercise training improves NO induced limb blood flow response at rest. The effect of exercise on the content of endothelial nitric oxide synthase (eNOS), the key enzyme in NO production, has not been investigated in muscle in vivo in humans. We hypothesize that there are reductions in eNOS expression and increases in muscle sympathetic tone in older individuals, resulting in reduced nitric oxide dependent skeletal muscle nutritive blood flow and alterations in muscle metabolism; furthermore, these age-associated NO-mediated changes can be counteracted, or reversed, by endurance exercise training. We will investigate 24 (20-30 yr) sedentary individuals (men and women), as well as 24 sedentary older (60-70 yr) individuals (men and women) in the sedentary state, as well as after one day and seven days of endurance exercise training. Ten of these sedentary older individuals will also be studied after an additional seven weeks of endurance training. A muscle biopsy will be taken to measure eNOS content, and nutritive skeletal muscle blood flow will be monitored using microdialysis under resting conditions. These investigations will determine if endurance exercise improves nitric oxide dependent nutritive blood flow in skeletal muscle at rest, and will determine if this improvement is associated with increases in eNOS in skeletal muscle biopsy samples. The mediation of NO-dependent vasodilation by muscle sympathetic tone, endothelin, and prostacyclin will also be investigated. The long-term objectives of these investigations are: 1) to identify mechanisms responsible for a reduced nitric oxide-dependent vasodilatation in older men and women and 2) to find practical means of reversing vasodilator decrements in older men and women, thereby reducing the incidence of cardiovascular-related diseases in this population.

描述（由申请人提供）：心血管疾病是美国死亡的主要原因，在60岁后心血管疾病的发生率迅速增加。心血管疾病的主要危险因素是高血压，这也增加了老年人的患病率。一氧化氮（NO）诱导的血管舒张随着年龄的增长而降低，导致血压升高和肢体血流降低，尤其是鉴于老年人的肌肉交感神经张力增加。 NO的产生受损也与周围血管疾病，胰岛素抵抗和2型糖尿病有关。但是，有一些证据表明，运动训练没有改善静止时的肢体流动反应。运动对无生产的关键酶（ENOS）含量的影响尚未在人类体内肌肉中进行研究。我们假设eNOS表达减少和老年人的肌肉交感神经张力增加，从而导致一氧化氮依赖的骨骼肌营养血液流量减少和肌肉代谢的改变；此外，这些与年龄相关的无介导的变化可以通过耐力运动训练来抵消或逆转。我们将研究24（20 - 30年）久坐的个体（男人和女性），以及久坐状态的24个久坐的年龄较大（60 - 70年）的人（60 - 70年），以及在一天和7天的耐力运动训练之后。经过七个星期的耐力训练，也将研究这些久坐的老年人中的十个。将进行肌肉活检以测量eNOS含量，并在静止条件下使用微透析来监测营养骨骼肌肉的血流。这些研究将确定耐力运动是否改善了静止骨骼肌的一氧化氮依赖性营养血流，并将确定这种改善是否与骨骼肌活检样品中eNOS的增加有关。还将研究肌肉交感神经，内皮素和前列环素的无依赖性血管舒张的介导。这些研究的长期目标是：1）确定导致老年男性和女性一氧化氮依赖性血管舒张的机制和2）找到逆转男性和女性血管舒张剂减少的实用方法，从而减少了这一人群心血管相关疾病的发生率。