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

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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.