EXAMINING THE VASCULAR TONE BAROREFLEX AS A TARGET FOR ALCOHOL USE INTERVENTION

描述(申请人提供)：这项申请寻求检查血管张力压力感受器反射作为一种生理机制，将酒精的血管活动与适应性行为改变联系起来。酒精以时间和剂量依赖的方式深刻而直接地影响血管，从而对血管的反应性产生负面影响。血管动力学异常具有深远的后果，部分原因是血管张力压力反射，它利用血管直径的变异性来补偿血压的急剧变化，并调节应激反应。血管张力压力感受器反射是一个闭环系统，通过自主神经和中枢神经系统之间的信息交换发挥作用。因此，可以通过直接评估血管张力压力反射活动来观察支持情绪自我调节和应激反应的生理和神经过程之间的相互关系。通过比较不饮酒者、适度饮酒者和重度饮酒者的血管压力感受器反射敏感性，还可以观察酒精如何扰乱这些相互关联的过程，并引发一连串的自我调节失败，从而增加使用酒精来应对情绪失调的风险。人们对血管张力压力反射系统知之甚少，因为直到最近，对搏动至搏动的血管张力变化的非侵入性评估并不准确。这项应用使用新技术和新方法来有效地表征血管张力压力反射系统的基本功能特性。具体地说，我们试图证实人类血管张力压力反射系统中存在共振，确定有效刺激共振振荡的范例，并探索酗酒和遗传背景如何影响血管张力压力反射敏感性。如果成功，这些创新研究将为一项研究计划提供基础，该计划将转化关于血管张力压力反射活动的基础科学发现，以开发适合广泛采用的临床相关治疗方法。该项目建立在首席研究人员先前成功应用有关心率压力反射系统共振频率的基本知识的基础上，开发了一种经验性支持的临床生物反馈程序，可降低与哮喘、重度抑郁、纤维肌痛、神经症和高血压相关的症状的严重程度。作为一种新的治疗靶点，通过生物反馈进行血管紧张压力感受性反射再训练，通过提供一种新的行为策略来帮助减少压力和负面情绪，可能与干预重度酒精摄入有关，旨在调节情绪唤醒。

DESCRIPTION (provided by applicant): This application seeks to examine the vascular tone baroreflex as a physiological mechanism that links the vascular actions of alcohol to adaptive behavior change. Alcohol profoundly and directly influences blood vessels to negatively affect vascular reactivity in a time- and dose-dependent manner. Abnormal vascular dynamics have far-reaching consequences due in part to the vascular tone baroreflex, which uses variability in blood vessel diameter to compensate for acute shifts in blood pressure and modulate stress reactions. The vascular tone baroreflex is a closed-loop system that functions via information exchange between the autonomic and central nervous systems. Thus, it is possible to observe the interrelationship of the physiological and neurological processes that support emotional self-regulation and stress responding by directly assessing vascular tone baroreflex activity. By comparing vascular tone baroreflex sensitivity in non- drinkers, moderate drinkers, and heavy drinkers, it may also be possible to observe how alcohol disrupts these interrelated processes and instigates the cascade of self-regulatory failures that enhance risk for using alcohol to cope with emotional dysregulation. Little is known about the vascular tone baroreflex system because, until recently, non-invasive assessment of changes in beat-to-beat vascular tone in response to perturbations was not accurate. This application uses new technology and new methodologies to validly characterize basic functional properties of the vascular tone baroreflex system. Specifically, we seek to confirm the presence of resonance in the vascular tone baroreflex system in humans, identify paradigms that effectively stimulate resonance oscillations, and explore how heavy drinking and genetic background affect vascular tone baroreflex sensitivity. If successful, these innovative studies will provide a foundation for a research program that translates basic science discoveries about vascular tone baroreflex activity to develop a clinically-relevant treatment amenable to wide-scale adoption. This project builds upon the principal investigator's prior success in applying basic knowledge about the resonance frequency in the heart rate baroreflex system to develop an empirically-supported clinical biofeedback procedure that reduces the severity of the symptoms associated with asthma, major depression, fibromyalgia, neurosis, and hypertension. As a novel therapeutic target, vascular tone baroreflex retraining through biofeedback has potential relevance for intervening in heavy alcohol use aimed at modulating emotional arousal by providing a novel behavioral strategy to help reduce stress and negative mood.