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: 10644031
• 负责人: Chueh-Lung Hwang
• 金额: $ 24.08万
• 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/10644031
• 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; 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 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。该申请将提供5年的职业发展 量身定制的计划是为了优化机会和发展独特的研究技能 在任何其他环境中镜像。在K99阶段，候选人将获得研究培训，并 酒精研究领域的专业发展。候选人将开发一项独特的研究 整合血管生理学，物理疗法和与酒精有关的人类健康的策略。这 候选人将采用该策略来解决有关升高机制的知识差距 收缩压（SBP）与针对中年成年人的暴饮暴食有关（50-64岁）。五分之一 中年成年人报告说暴饮暴食，有一半以上报告患有高血压。但是，这个年龄 在酒精研究中已经研究了小组。在健康的年轻人（18-30年）中，正常SBP 候选人发现重复的暴饮暴食与微血管功能的降低有关 作为小型动脉中流动诱导的血管舒张（FIV）。候选人还发现重复 暴饮暴食与泌尿肾上腺素，血管收缩和标记的水平升高有关 交感神经活动。在后来的中期阶段，反复饮酒和衰老的协同作用 可能会加剧FIV和交感神经活动的这些不利变化，从而导致SBP升高。提议 研究将确定重复饮酒对微血管功能，交感神经和 中年成年人的血压以及这些不良变化的可逆性。 AIM 1将决定角色 去甲肾上腺素是与反复饮酒相关的动脉FIV减少的潜在主持人。 FIV将在耐药性动脉（SBP的主要调节部位）中测量 生活成人暴饮暴食者与戒酒者/中度饮酒者。 AIM 2将决定交感神经 在中年成人暴饮暴食者与SBP（直接通过微功能学）和SBP（静止和卧床）的活动 戒酒者/中度饮酒者。这种方法的发现将有可能建立治疗靶标 为了对升高的SBP贡献，对理解具有更广泛的影响 中年成年人的高血压发展。这些发现还将启动独立的R00阶段 在AIM 3中研究候选人将研究高强度间隔的可行性和有效性 改善FIV和减少交感神经活动的培训，从而减少了中年狂欢的SBP 饮酒者。临床和机械数据将为R01的研究奠定基础 酒精诱导的SBP升高，并侧重于微血管功能和交感神经活动。 该研究对了解中年的心血管风险发展机制具有很大的影响 成人，对美国国家酒精滥用和酒精中毒研究所的使命非常有反应。

项目成果

The physiological benefits of sitting less and moving more: Opportunities for future research.

• DOI: 10.1016/j.pcad.2020.12.010
• 发表时间: 2022-07
• 期刊: Progress in cardiovascular diseases
• 影响因子: 9.1
• 作者: Hwang CL;Chen SH;Chou CH;Grigoriadis G;Liao TC;Fancher IS;Arena R;Phillips SA
• 通讯作者: Phillips SA

Time to Promote the Awareness of Unhealthy Alcohol Use Among Women.

是时候提高女性对不健康饮酒的认识了。

• DOI: 10.1089/jwh.2021.0546
• 发表时间: 2022
• 期刊: Journal of women's health (2002)
• 作者: Hwang,Chueh-Lung;Phillips,ShaneA;Tu,Min-Hsuan;Piano,MariannR
• 通讯作者: Piano,MariannR

Blood Pressure and Arterial Stiffness after a Maximal Aerobic Exercise in Young Adult Binge Drinkers and Moderate Drinkers.

青年酗酒者和适度饮酒者进行最大有氧运动后的血压和动脉僵硬。

• 发表时间: 2022
• 期刊: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• 作者: Jackson,Ronald;Tawade,Samiksha;Drab,Yuliya;Baynard,Tracy;Clifford,Philip;Piano,Mariann;Phillips,Shane;Hwang,Chueh-Lung
• 通讯作者: Hwang,Chueh-Lung