Neurovascular Control of Renal Blood Flow During Exercise in African American Adults

项目摘要 非裔美国人（AA）成年人发生心血管和肾脏疾病（CVRD）的风险高于 白色（W）成年人。交感神经系统活动升高，通常发生在对应激源的反应中， 与CVRD发生率增加相关。体力消耗，如运动，急剧增加 针对肾脏的交感神经系统活动，导致肾血管收缩， 减少肾血流量（RBF）。有限的研究表明，健康的年轻AA成年人表现出夸大的 在静息和交感神经激活期间的交感神经反应性，这可能是 这一人群中CVRD的风险增加。然而，急性肾血管收缩反应，任何 迄今为止尚未在AA成人中研究交感神经系统激活。在同情 神经系统激活，例如运动、针对肾脏和/或肾脏的交感神经活动， 在AA成人中，由此产生的血管反应可能被夸大，导致更大的肾血管收缩 和更大的RBF减少。随着时间的推移，这种对交感神经激活的夸大的神经血管反应 可能会对肾脏产生负面的累积效应，这可能是导致更大的 该人群中CVRD的发病率。因此，本建议旨在检查肾血管收缩剂 在CVRD发生之前，健康AA成人对交感神经应激源的反应，这将实现 通过两个具体目标。我们的第一个目的是确定肾血管收缩反应的急性动态运动 健康年轻的AA成年人与健康年轻的W成年人相比。具体来说，我们将使用最先进的 方法测量静息和急性骑自行车运动时的RBF速度和BP，以计算肾血管 抵抗运动的反应。我们将检验健康的年轻AA成年人表现出 与健康的年轻W成人相比，急性骑自行车运动的肾血管收缩反应过度。在 我们的第二个目的是评估肾血管收缩反应，非运动交感神经应激， 健康的年轻AA成年人与健康的年轻W成年人相比。具体来说，我们将测量RBF速度， 静息时、冷加压和精神应激试验期间的血压，以计算肾血管阻力反应， 这些非运动应激源，以测试假设，健康的年轻AA成人表现出夸大的肾脏 血管收缩反应非运动交感神经应激相比，健康的年轻W成人。我们将 使用多普勒超声的高度创新方法来测量运动和非运动期间的RBF 交感神经应激源非侵入性和高时间分辨率，以完成这些特定的目标。这 我们经验丰富的研究团队的一种新方法，用于评估肾血管收缩剂对交感神经的反应， 在成人AA的压力将提供新的，机械的见解，在这个研究不足，但临床上有意义的领域。 该项目的发现将促进我们对AA成人CVRD风险升高的原因的理解， 对今后预防CVRD的影响。

Project Summary African American (AA) adults have a greater risk for developing cardiovascular and renal disease (CVRD) than White (W) adults. Elevated sympathetic nervous system activity, usually occurring in response to stressors, is associated with increased incidence of CVRD. Physical exertion, such as exercise, acutely increases sympathetic nervous system activity directed towards the kidneys, resulting in renal vasoconstriction and reduced renal blood flow (RBF). Limited research shows that healthy young AA adults exhibit exaggerated sympathetic responsiveness both at rest and during sympathetic activation, which may be a major contributor to the increased risk of CVRD in this population. However, the acute renal vasoconstrictor response to any sympathetic nervous system activation has not been investigated to date in AA adults. During sympathetic nervous system activation such as exercise, sympathetic neural activity directed to the kidneys and/or the resultant vascular response might be exaggerated in AA adults, contributing to greater renal vasoconstriction and a larger reduction in RBF. Over time, this exaggerated neurovascular response to sympathetic activation could have a negative cumulative effect on the kidneys, which could be a contributing factor to the greater incidence of CVRD in this population. Therefore, this proposal aims to examine the renal vasoconstrictor response to sympathetic stressors in healthy AA adults prior to development of CVRD, which will be achieved via two specific aims. Our first aim is to determine the renal vasoconstrictor response to acute dynamic exercise in healthy young AA adults compared to healthy young W adults. Specifically, we will use state-of-the-art methods to measure RBF velocity and BP at rest and during acute cycling exercise to calculate renal vascular resistance responses to exercise. We will test the hypothesis that healthy young AA adults exhibit an exaggerated renal vasoconstrictor response to acute cycling exercise compared to healthy young W adults. In our second aim, we will assess the renal vasoconstrictor response to non-exercise sympathetic stressors in healthy young AA adults compared to healthy young W adults. Specifically, we will measure RBF velocity and BP at rest and during cold pressor and mental stress tests to calculate renal vascular resistance responses to these non-exercise stressors to test the hypothesis that healthy young AA adults exhibit exaggerated renal vasoconstrictor responses to non-exercise sympathetic stressors compared to healthy young W adults. We will use the highly innovative approach of Doppler ultrasound to measure RBF during exercise and non-exercise sympathetic stressors non-invasively and with high temporal resolution to complete these specific aims. This novel approach by our experienced research team to assess the renal vasoconstrictor response to sympathetic stressors in AA adults will provide new, mechanistic insights in this understudied yet clinically significant area. The findings from this project will advance our understanding of why AA adults have elevated CVRD risk, with implications for future efforts toward prevention of CVRD.