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

基本信息

批准号：
6649673
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
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-01 至 2005-07-31
项目状态：
已结题

项目摘要

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（申请人提供）：心血管疾病是美国的首要死因，60岁以后心血管疾病的发病率迅速增加。心血管疾病的主要危险因素是高血压，老年人的患病率也会增加。一氧化氮（NO）引起的血管舒张随着年龄的增长而减少，导致血压升高和肢体血流量减少，特别是考虑到老年人的肌肉交感神经张力增加。 NO 产生受损还与周围血管疾病、胰岛素抵抗和 2 型糖尿病有关。然而，有一些证据表明运动训练可以改善休息时一氧化氮诱导的肢体血流反应。运动对内皮型一氧化氮合酶 (eNOS) 含量的影响尚未在人体肌肉中进行研究，内皮型一氧化氮合酶是 NO 产生的关键酶。我们假设老年人的 eNOS 表达减少，肌肉交感神经张力增加，导致一氧化氮依赖性骨骼肌营养性血流减少和肌肉代谢改变；此外，这些与年龄相关的一氧化氮介导的变化可以通过耐力运动训练来抵消或逆转。我们将调查 24 名（20-30 岁）久坐的个体（男性和女性），以及 24 名久坐的老年人（60-70 岁）个体（男性和女性）在久坐状态下以及一天和 7 天后的情况的耐力运动训练。在额外七周的耐力训练后，还将对其中十名久坐的老年人进行研究。将进行肌肉活检来测量 eNOS 含量，并在静息条件下使用微透析监测营养性骨骼肌血流量。这些研究将确定耐力运动是否改善静止时骨骼肌中一氧化氮依赖性营养性血流，并将确定这种改善是否与骨骼肌活检样本中 eNOS 的增加有关。还将研究肌肉交感神经张力、内皮素和前列环素对 NO 依赖性血管舒张的介导。这些研究的长期目标是：1）确定老年男性和女性中一氧化氮依赖性血管舒张减少的机制；2）找到逆转老年男性和女性血管舒张减少的实用方法，从而降低发病率该人群中心血管相关疾病的发生率。