Alcohol and Neurovascular Control in Humans

项目摘要 人们普遍认识到，“酗酒"与心血管疾病的增加有关。 风险，但这在很大程度上是基于流行病学研究和机制仍然知之甚少。 交感神经过度活跃被认为是酒精介导的心血管疾病的潜在机制。 疾病，但缺乏直接证据。拟议的项目是我们追求长期- 长期目标是探索酒精介导的高血压、中风和心源性猝死， 可能降低这些心血管疾病发病率的干预措施。拟议项目的重点 晚上饮酒对夜间和清晨自主神经功能的影响， 男性和女性酗酒者的反应。在目标1中，将确定晚上饮酒的影响 夜间自主控制和交感神经反应的第二天早上。目标2将 确定性别（男性与女性）和卵巢周期（卵泡早期与黄体中期）对 交感神经对晚间酒精的反应目标3将确定是否连续阳性 气道压力（CPAP）在夜间和清晨减弱酒精介导的交感神经兴奋。一个 探索性目的是确定对酒精和CPAP的自主反应是否与情感状态相关 和心理表现。我们的中心假设是，晚上饮酒会引起 交感神经在晚上和第二天早上过度活跃，这种交感神经兴奋将是 经CPAP治疗后，女性增大，变钝。本项目的新奇和创新性在于， 机械目标得到了干预目标的支持，包括随机对照试验（CPAP与 假CPAP）。该项目利用已建立的黄金标准方法来评估睡眠（多导睡眠图） 和交感神经活动和反应性（显微神经描记术）。总之，本项目将确定 模拟“狂饮”酒精对高血压时神经心血管功能的影响 心血管风险（即，睡眠和清晨）在男性和女性酗酒者，并测试一个潜在的 治疗策略（即，CPAP），以减轻酒精引起的自主神经功能障碍。

Project Summary There is wide-spread recognition that `binge' alcohol consumption is associated with increased cardiovascular risk, but much of this is based on epidemiological studies and mechanisms remain poorly understood. Sympathetic overactivity has been suggested as a potential mechanism for alcohol-mediated cardiovascular disease, but direct evidence is lacking. The proposed project represents our first step in the pursuit of a long- term goal to explore alcohol-mediated hypertension, stroke, and sudden cardiac death, and practical interventions that might reduce the incidence of these cardiovascular conditions. The proposed project focuses on the impact of evening alcohol consumption on nocturnal and early morning autonomic function and reactivity in male and female binge drinkers. In aim 1, will determine the effect of evening alcohol consumption on nocturnal autonomic control and sympathetic neural responsiveness the subsequent morning. Aim 2 will determine the influence of sex (male vs. female) and the ovarian cycle (early follicular vs. midluteal phase) on sympathetic neural responsiveness to evening alcohol in humans. Aim 3 will determine if continuous positive airway pressure (CPAP) blunts alcohol-mediated sympathoexcitation at night and early morning. An exploratory aim will determine if autonomic responses to alcohol and CPAP are associated with affective states and psychomotor performance. Our central hypothesis is that evening alcohol consumption will elicit sympathetic overactivity at night and the subsequent morning, and that this sympathoexcitation will be augmented women and blunted after CPAP treatment. The novelty and innovation of this project is that our mechanistic aims are bolstered with an interventional aim that includes a randomized, control trial (CPAP vs. sham-CPAP). The project utilizes established, gold-standard methods for assessing sleep (polysomnography) and sympathetic neural activity and reactivity (microneurography). In summary, this project will determine the impact of simulated `binge' alcohol consumption on neural cardiovascular function at times of elevated cardiovascular risk (i.e., sleep and early morning) in male and female binge drinkers, and test a potential therapeutic strategy (i.e., CPAP) to blunt alcohol-induced autonomic dysfunction.