Vascular and Neuro-Inflammatory Effects of Endurance Exercise Training in African

描述(由申请人提供)： 非洲裔美国人比高加索人患高血压、心血管疾病、中风和肾脏疾病的风险更大。这可能与非裔美国人的动脉功能障碍有关，包括动脉僵硬和阻力动脉微血管反应性降低。此外，非洲裔美国人的炎症标志物水平更高，对各种应激源的交感兴奋反应更强。交感神经和副交感神经激活减少之间的这种失衡可能直接影响血管功能，增强更大的炎症反应，进一步改变血管壁的关键结构和功能特性。这项建议的总体目标是测试耐力运动训练对动脉结构和功能的影响，并检查与高加索人相比，年轻的非裔美国人(18-35岁)动脉结构和功能发生变化的潜在机制。我们将在干预前后的时间点检测静息和低强度(次最大循环测功法)和高强度(最大循环测功法)交感神经兴奋后的这些影响，因为交感神经兴奋可能解释在静息时不明显的变化。由于非裔美国人的动脉僵硬程度更高，微血管反应性更低，对交感神经兴奋的反应更强，炎症标志物水平更高，血管收缩张力更强，我们假设，与匹配的高加索人组相比，非裔美国人将受益更多(例如，在运动训练中表现出更大的变化)，并且在取消训练后保持这些变化的时间更长。我们的具体目标将测试：1)耐力训练对静息和急性交感兴奋后动脉僵硬、导管动脉和微血管反应性的影响；2)耐力训练对动脉重构的影响；3)耐力训练对自主神经功能和炎症标志物的影响。我们将采用纵向设计，控制期、运动期和非训练期的长度相等(8周)。受试者将在第0周(基线)、第8周(在控制期之后)、第16周(在运动干预之后)和第24周(在去训练期之后)进行测试。受试者将在每个测试点进行3天不同的测试，以测量对两种不同的交感兴奋刺激(最大和次最大运动)的反应。我们将使用混合模型实验设计，使用分段线性多水平模型比较在群体(非裔美国人和高加索人)和纵向在四个时间点收集的数据。这个项目可能会产生巨大的公共卫生影响，记录非裔美国人耐力训练的预防效果，并将提供重要的机械性见解，了解耐力训练在改善非裔美国人和高加索年轻人的动脉、自主和炎症状态方面所起的作用。公共卫生相关性：血管和自主神经功能以及炎症是心血管死亡和发病率的预测因子，是高血压、心血管疾病、中风和肾脏疾病的先兆和贡献者。非洲裔美国人比白人患上这些疾病的风险更大。该项目评估耐力运动训练作为一种预防性行为干预措施的效果，以降低非洲裔美国年轻人患这些疾病的风险。

DESCRIPTION (provided by applicant): African-Americans are at greater risk than Caucasians for developing hypertension, cardiovascular disease, stroke and renal disease. This is likely related to arterial dysfunction including greater arterial stiffness, and reduced microvascular reactivity of resistance arteries in African-Americans. In addition, African-Americans have higher levels of inflammatory markers, and a greater sympathoexcitatory response to various stressors. This imbalance between sympathetic and reduced parasympathetic activation may directly affect vascular function and potentiate a greater inflammatory response, further altering key structural and functional properties of the vascular wall. The overall aim of this proposal is to test the effects of endurance exercise training on arterial structure and function, and to examine potential mechanisms producing changes in arterial structure and function in young (18-35 years of age) African Americans when compared to Caucasians. We will examine these effects at rest and following a low intensity (submaximal cycle ergometry) and high intensity (maximal cycle ergometry) sympathoexcitation at both pre- and post-intervention time points, since sympathoexcitation may elucidate changes not evident at rest. Because African-Americans have higher levels of arterial stiffness, lower microvascular reactivity, greater responses to sympathoexcitation, greater levels of inflammatory markers and greater vasoconstrictive tone, we hypothesize that African-Americans will benefit more (e.g. show greater changes in response to exercise training) and retain these changes longer following de-training, when compared to a matched group of Caucasians. Our specific aims will test: 1) the effects of endurance training on arterial stiffness, conduit artery and microvascular reactivity at rest and following acute sympathoexcitation; 2) the effects of endurance training on arterial remodeling; 3) the effects of endurance training on autonomic function and markers of inflammation. We will utilize a longitudinal design with control, exercise and detraining periods of equal length (8 weeks). Subjects will be tested during week 0 (baseline), at week 8 (following the control period), at week 16 (following the exercise intervention), and again at week 24 (after the de-training period). Subjects will be tested on 3 different days at each testing point, to allow for measuring the response to the two different sympathoexcitatory stimuli (maximal and submaximal exercise). We will utilize a mixed-model experimental design comparing data collected on groups (African-Americans and Caucasians) and longitudinally at four time points using Piecewise Linear Multilevel Modeling. This project will have potentially large public health effects documenting the preventive effects of endurance training in African- Americans, and will provide important mechanistic insight into the role that endurance training plays in improving arterial, autonomic and inflammatory status in young African-Americans and Caucasians. PUBLIC HEALTH RELEVANCE: Vascular and autonomic function, and inflammation are predictors of cardiovascular mortality and morbidity and are precursors of, and contributors to, hypertension, CVD, stroke and renal disease. African-Americans are at greater risk than Caucasians for developing these diseases. This project evaluates the effect of endurance exercise training as a preventive behavioral intervention to lower the risk of these diseases in young African-Americans.