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）：本申请旨在检查血管张力压力反射作为将酒精的血管作用与适应性行为变化联系起来的生理机制。酒精深刻而直接地影响血管，以时间和剂量依赖性方式对血管反应性产生负面影响。异常的血管动力学具有深远的影响，部分原因是血管张力压力反射，它利用血管直径的变化来补偿血压的急剧变化并调节应激反应。血管张力压力反射是一个闭环系统，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，通过直接评估血管张力压力反射活动，可以观察支持情绪自我调节和压力反应的生理和神经过程的相互关系。通过比较不饮酒者、中度饮酒者和重度饮酒者的血管张力压力反射敏感性，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，从而增加使用酒精应对情绪的风险。失调。人们对血管张力压力感受反射系统知之甚少，因为直到最近，对逐搏血管张力响应扰动变化的无创评估并不准确。该应用程序使用新技术和新方法来有效表征血管张力压力反射系统的基本功能特性。具体来说，我们试图确认人类血管张力压力反射系统中共振的存在，确定有效刺激共振振荡的范式，并探索大量饮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奠定基础，该计划将有关血管紧张压力反射活动的基础科学发现转化为开发适合广泛采用的临床相关治疗方法。该项目建立在主要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开发经验支持的临床生物反馈程序的基础上，该程序可减轻与哮喘、重性抑郁、纤维肌痛、神经症、和高血压。作为一种新的治疗目标，通过生物反馈进行血管张力压力反射再训练对于干预重度饮酒具有潜在的相关性，旨在通过提供一种新的行为策略来帮助减轻压力和负面情绪来调节情绪唤醒。 公众健康相关性：血管直径的变异性是健康的一个基本特征。就像动脉粥样硬化（血管壁硬化）是美国主要的死亡原因一样，大量饮酒会导致这种变异性的丧失。在此应用中，我们将检查控制血管直径变异的血管张力压力反射系统，并探讨大量饮酒如何影响其敏感性。我们还将探讨一个人的基因构成如何影响该系统的功能。