Reducing blood pressure in mid-life adult binge drinkers: the role of microvascular function and sympathetic activity

降低中年成人酗酒者的血压：微血管功能和交感神经活动的作用

• 批准号: 10544198
• 负责人: Chueh-Lung Hwang
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10544198
• 关键词: Address; Adult; Aerobic Exercise; Age; Aging; Alcohols; Area; Arteries; Attention; Biopsy; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular Physiology; Clinical; Data; Development; Development Plans; Effectiveness; Environment; Event; Fatty acid glycerol esters; Foundations; Goals; Health; Hour; Human; Hypertension; Interval training; Intervention; Knowledge; Measures; Microvascular Dysfunction; Mission; National Institute on Alcohol Abuse and Alcoholism; Nerve; Norepinephrine; Phase; Physical therapy; Physiology; Population; Prevention Research; Public Health; Recording of previous events; Reporting; Research; Research Personnel; Research Training; Resistance; Rest; Role; Site; Supervision; Therapeutic; Training; United States; United States National Institutes of Health; Urine; Vasoconstrictor Agents; Vasodilation; age group; age related; alcohol abstinence; alcohol research; binge drinker; binge drinking; blood pressure elevation; blood pressure intervention; blood pressure reduction; cardiovascular risk factor; career; career development; early onset; effective intervention; exercise intervention; exercise training; fitness; improved; longitudinal design; middle age; normal aging; prevent; randomized controlled design; receptor; response; skills; therapeutic target; urinary; vascular injury; vasoconstriction; young adult

The candidate is committed to identifying/developing preventative and therapeutic approaches for alcohol- induced hypertension and cardiovascular disease. This application will provide a 5-year career development plan which has been tailored to optimize opportunities and to develop unique research skills that could not be mirrored in any other environment. During the K99 phase, the candidate will obtain research training and professional development in the field of alcohol research. The candidate will develop a unique research strategy that integrates vascular physiology, physical therapies and alcohol-related human health. The candidate will apply the strategy to address the gaps in knowledge of the mechanisms underlying elevated systolic blood pressure (SBP) associated with binge drinking targeting mid-life adults (50-64 years). One fifth of mid-life adults reported binge drinking and more than half reported having hypertension. However, this age group has been understudied in alcohol research. In healthy young adults (18-30 years) with normal SBP, the candidate has found that repeated binge drinking is associated with reduced microvascular function, measured as flow-induced vasodilation (FIV) in small resistance arteries. The candidate has also found that repeated binge drinking is associated with increased levels of urinary norepinephrine, a vasoconstrictor and a marker of sympathetic nerve activity. In a later mid-life stage, the synergistic effect of repeated binge drinking and aging may aggravate these adverse changes in FIV and sympathetic activity, causing elevated SBP. The proposed study will determine the effect of repeated binge drinking on microvascular function, sympathetic activity, and blood pressure in mid-life adults and the reversibility of these adverse changes. Aim 1 will determine the role of norepinephrine as a potential moderator of reduced arteriolar FIV associated with repeated binge drinking. FIV will be measured in resistance arteries, the major regulatory site of SBP, isolated from fat biopsies of mid- life adult binge drinkers vs. alcohol abstainers/moderate drinkers. Aim 2 will determine sympathetic nerve activity (directly via microneurography) and SBP (resting and ambulatory) in mid-life adult binge drinkers vs. alcohol abstainers/moderate drinkers. The findings of this approach will potentially establish therapeutic targets for alcohol-attributable contribution to elevated SBP and have broader implications for understanding hypertension development in mid-life adults. The findings will also launch the R00 phase of independent research where in Aim 3 the candidate will investigate the feasibility and effectiveness of high-intensity interval training on improving FIV and reducing sympathetic activity, thereby reducing SBP in mid-life adult binge drinkers. The clinical and mechanistic data will build the foundation for an R01 studying the mechanisms of alcohol induced elevated SBP, and an intervention focusing on microvascular function and sympathetic activity. The study has high impact for understanding the mechanisms of cardiovascular risk development in mid-life adults and is highly responsive to the mission of the National Institute on Alcohol Abuse and Alcoholism.

候选人致力于识别/开发酒精的预防和治疗方法 诱发高血压和心血管疾病。该应用程序将提供 5 年的职业发展机会 该计划旨在优化机会并发展独特的研究技能，这是无法实现的 镜像到任何其他环境中。在K99阶段，候选人将获得研究培训和 酒精研究领域的专业发展。候选人将开展独特的研究 整合血管生理学、物理疗法和与酒精相关的人类健康的策略。这 候选人将应用该策略来解决对高水平潜在机制的知识差距 与中年成年人（50-64 岁）酗酒相关的收缩压（SBP）。五分之一 中年成年人报告酗酒，超过一半报告患有高血压。然而这个年纪 该小组一直在酒精研究方面进行深入研究。在 SBP 正常的健康年轻人（18-30 岁）中， 候选人发现，反复酗酒与微血管功能下降有关，经测量 如小阻力动脉中的血流诱导血管舒张（FIV）。候选人还发现，重复 酗酒与尿去甲肾上腺素水平升高有关，去甲肾上腺素是一种血管收缩剂，也是酒精中毒的标志物。 交感神经活动。在中年后期，反复酗酒和衰老的协同效应 可能会加剧 FIV 和交感神经活动的这些不利变化，导致 SBP 升高。拟议的 研究将确定反复酗酒对微血管功能、交感神经活动和 中年成年人的血压以及这些不良变化的可逆性。目标 1 将确定角色 去甲肾上腺素作为与反复酗酒相关的小动脉 FIV 减少的潜在调节剂。 FIV 将在阻力动脉中测量，阻力动脉是 SBP 的主要调节部位，从中年脂肪活检中分离出来。 生活中的成人酗酒者与戒酒者/适度饮酒者。目标 2 将确定交感神经 中年成人酗酒者与正常饮酒者的活动（直接通过显微神经造影）和收缩压（静息和动态） 戒酒者/适度饮酒者。这种方法的发现可能会确定治疗目标 酒精对收缩压升高的影响并对理解具有更广泛的影响 中年成人高血压的发展。研究结果还将启动独立研究的 R00 阶段 研究目标 3 中考生将调查高强度间歇训练的可行性和有效性 改善 FIV 和减少交感神经活动的培训，从而降低中年成人暴饮暴食时的 SBP 饮酒者。临床和机制数据将为 R01 研究机制奠定基础 酒精引起收缩压升高，以及针对微血管功能和交感神经活动的干预。 该研究对于理解中年心血管风险发展机制具有重大影响 成年人，对国家酒精滥用和酒精中毒研究所的使命高度敏感。