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

检查血管张力压力反射作为酒精使用干预的目标

• 批准号: 8241500
• 负责人: Evgeny G. Vaschillo
• 金额: $ 22.22万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-05 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8241500
• 关键词: Acute; Adaptive Behaviors; Adoption; Affect; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Applications Grants; Arousal; Asthma; Atherosclerosis; Baroreflex; Basic Science; Behavior; Behavioral; Biofeedback; Blood Pressure; Blood Vessels; Blood flow; Calcium; Caliber; Cardiovascular system; Cause of Death; Characteristics; Chronic; Clinical; DNA; Development; Dose; Emotional; Equilibrium; Failure; Fibromyalgia; Foundations; Frequencies; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genomics; Genotype; Health; Heart Rate; Heavy Drinking; Human; Hypertension; Individual; Informal Social Control; Intervention; Investigation; Knowledge; Link; Major Depressive Disorder; Measures; Methodology; Methods; Modeling; Muscle Cells; Neuraxis; Neurologic; Neurotic Disorders; Participant; Persons; Physiologic pulse; Physiological; Potassium; Potassium Channel; Principal Investigator; Procedures; Process; Property; Reaction; Research; Risk; Severities; Single Nucleotide Polymorphism; Stress; Symptoms; System; Testing; Time; Translating; United States; Vascular Smooth Muscle; autonomic reflex; base; behavior change; biological adaptation to stress; clinically relevant; data mining; drinking behavior; innovation; large-conductance calcium-activated potassium channels; negative mood; new technology; new therapeutic target; novel; programs; reduced alcohol use; response; stressor; success; tool; use alcohol to cope; vasoconstriction; young adult

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. PUBLIC HEALTH RELEVANCE: Variability in blood vessel diameter is an essential feature of health. Like atherosclerosis (hardening of the vessel walls), which is the leading cause of death in the United State, heavy drinking leads to a loss of this variability. In this application, we will examine the vascular tone baroreflex system, which controls blood vessel diameter variability, and explore how heavy drinking affects its sensitivity. We will also explore how a person's genetic makeup can influence the functioning of this system.

描述（由申请人提供）：本申请试图将血管纹状反射作为一种生理机制，将酒精的血管作用与适应性行为变化联系起来。酒精深刻并直接影响血管以时间和剂量依赖性方式对血管反应产生负面影响。异常血管动力学具有深远的影响，部分原因是血管张力骨反射，该血管使用血管直径的变异性来补偿血压的急性转移并调节应力反应。血管色调BaroreFlex是一个闭环系统，可通过自主神经系统和中枢神经系统之间的信息交换发挥作用。因此，有可能观察生理和神经系统过程的相互关系，这些过程通过直接评估血管张力刺激性活性来支持情绪自我调节和压力反应。通过比较非饮酒者，中等饮酒者和繁重饮酒者的血管张力敏感性，也可以观察到酒精如何破坏这些相互关联的过程，并激发一系列的自我调节失败，从而增强使用酒精来应对情绪失调的风险。关于血管张力的压力反射系统知之甚少，因为直到最近，响应扰动而对节拍到伴侣血管张力的变化的不侵入性评估尚不准确。该应用程序使用新技术和新方法来有效地表征血管音的基本功能属性。具体而言，我们寻求确认人类血管张力型压力反射系统中的共振，确定有效刺激共振振荡的范式，并探索繁重的饮酒和遗传背景如何影响血管张力的baroreflex敏感性。如果成功的话，这些创新研究将为研究计划提供基础，该研究计划将基础科学发现有关血管张力的Baroreflex活动，以开发与广泛采用的临床相关治疗。该项目基于主要研究者的先前成功，以应用有关心率的触压力反射系统中的谐振频率的基本知识，以开发经验支持的临床生物反馈程序，从而降低了与哮喘，大抑郁症，纤维肌痛，神经症，神经病和高血压相关的症状严重程度。作为一个新颖的治疗靶标，通过生物反馈进行血管张力润滑性重新培训具有潜在的相关性，即通过提供一种新型的行为策略来帮助减轻压力和负面情绪，旨在调节旨在调节情绪唤醒的重型酒精使用。 公共卫生相关性：血管直径的变异性是健康的重要特征。就像动脉粥样硬化（血管壁的硬化）一样，这是美国死亡的主要原因，大量饮酒会导致这种变异性丧失。在此应用中，我们将检查控制血管直径变异性的血管张力刺激系统，并探讨饮酒如何影响其敏感性。我们还将探讨一个人的遗传构成如何影响该系统的功能。