Resistance Training Improvement in Age-Associated Endothelial Dysfunction

抗阻训练改善年龄相关内皮功能障碍

• 批准号: 7778104
• 负责人: MICHAEL B HARRIS
• 金额: $ 21.2万
• 依托单位: COLLEGE OF WILLIAM AND MARY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7778104
• 关键词: Accounting; Age; Aging; Animals; Aorta; Biological Availability; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Chronic; Co-Immunoprecipitations; Coronary Arteriosclerosis; Diabetes Mellitus; Elderly; Event; Exercise; Functional disorder; Generations; Heart failure; Human; Hypertension; Immunoblotting; Light; Measures; Modeling; Molecular; Muscle; Obesity; Oxidative Stress; Play; Post-Translational Protein Processing; Preparation; Proteins; Rattus; Resistance; Risk; Role; Source; Superoxides; Testing; Tissues; Training; Training Programs; Tyrosine; United States; Vasodilation; aged; arteriole; cardiovascular disorder risk; human subject; hypercholesterolemia; improved; inhibitor/antagonist; nitration; normal aging; prevent; public health relevance; strength training; vascular bed

DESCRIPTION (provided by applicant): Aging is associated with a decline in endothelial function which in-turn is a precursor to many adverse cardiovascular events. Numerous studies have shown that endurance exercise training enhances vascular function in both normal and aged humans and animals as well as under pathological conditions such as chronic heart failure, coronary artery disease, hypertension, hypercholesterolemia, obesity, and diabetes. Despite the evidence for exercise-induced improvements in vascular function in aged models, few of these studies have examined the effects of resistance training on vascular function. In addition, the few studies examining the effects of resistance training have primarily involved human subjects in which the molecular mechanisms of the improved endothelial function were not determined. One of the primary molecular mechanisms believed to play a role in endurance exercise induced improvement in vascular function is a decrease in superoxide formation and a concomitant increase in NO bioavailability. In light of these observations we will examine whether an 8 week resistance training program in rats will improve NO- dependent vasorelaxation in the aorta, femoral and resistance arterioles of aged animals using isolated vascular rings and cannulated, pressurized vessel preparations. Furthermore, we will examine changes in superoxide formation and protein tyrosine nitration in these vessels to determine if resistance exercise like endurance exercise reduces vascular oxidative stress. Potential cellular sources of superoxide generation and oxidative stress will also be explored using pharmacological inhibitors of superoxide and measures of superoxide formation. Finally, we will examine whether changes in eNOS expression or posttranslational modifications of eNOS can account for the improvements in endothelial function and reduction of oxidative stress in vessels from resistance trained, aged rats using co-immunoprecipitation and immunoblotting of these vascular tissues. Aim 1. To test the hypothesis that resistance exercise training will improve age-associated endothelial dysfunction in different vascular beds. Aim 2. To test the hypothesis that resistance exercise reduces vascular oxidative stress in young and old animals. Aim 3. To test the hypothesis that increases in NOS expression and posttranslational modifications of eNOS are transiently altered over the course of a chronic resistance exercise training program. PUBLIC HEALTH RELEVANCE: Cardiovascular disease is the leading cause of death in the United States and worldwide and the risk of having cardiovascular disease increases with age. Aging is also associated with a decline in muscular strength and mobility which can be prevented by resistance exercise training; however, it is unknown whether this type of training like endurance training can also reduce the risk of cardiovascular disease. This project will examine potential mechanisms by which resistance exercise training can reduce the risk of cardiovascular disease associated with advancing age.

描述（由申请人提供）：衰老与内皮功能下降相关，而内皮功能下降又是许多不良心血管事件的前兆。许多研究表明，耐力运动训练增强正常和老年人和动物的血管功能，以及在病理条件下，如慢性心力衰竭，冠状动脉疾病，高血压，高胆固醇血症，肥胖症和糖尿病。尽管有证据表明运动诱导的老年模型血管功能的改善，这些研究中很少有研究阻力训练对血管功能的影响。此外，少数研究阻力训练的影响主要涉及人类受试者，其中改善内皮功能的分子机制尚未确定。据信在耐力运动诱导的血管功能改善中起作用的主要分子机制之一是超氧化物形成的减少和伴随的NO生物利用度的增加。根据这些观察结果，我们将使用分离的血管环和插管的加压血管制剂来检查大鼠中8周的阻力训练计划是否会改善老年动物的主动脉、股动脉和阻力小动脉中的NO依赖性血管舒张。此外，我们将检查这些血管中超氧化物形成和蛋白质酪氨酸硝化的变化，以确定耐力运动等抗阻运动是否能降低血管氧化应激。超氧化物生成和氧化应激的潜在细胞来源也将使用超氧化物的药理学抑制剂和超氧化物形成的措施进行探索。最后，我们将研究是否eNOS表达或eNOS的翻译后修饰的变化可以解释血管内皮功能的改善和减少氧化应激的阻力训练，老年大鼠使用免疫共沉淀和免疫印迹这些血管组织。目标1.验证抗阻运动训练可改善不同血管床年龄相关内皮功能障碍的假设。目标2.为了验证抗阻运动降低年轻和老年动物血管氧化应激的假设。目标3.为了验证这一假设，即在一个慢性阻力运动训练计划的过程中，NOS的表达和eNOS的翻译后修饰的增加是暂时改变。 公共卫生关系：心血管疾病是美国和世界范围内的主要死亡原因，患心血管疾病的风险随着年龄的增长而增加。衰老也与肌肉力量和运动能力的下降有关，这可以通过阻力运动训练来预防;然而，目前尚不清楚这种类型的训练是否也可以降低心血管疾病的风险。该项目将研究抗阻运动训练可以降低与年龄增长相关的心血管疾病风险的潜在机制。