The overall goals of this application are to 1) provide the applicant mentored research training and professional development as an independent investigator; and 2) address the gap in knowledge of how sex impacts the effect of binge drinking on blood pressure and arterial function. Binge drinking, or episodic excessive alcohol use, is associated with increased systolic blood pressure (SBP) and reduced arterial function, which both are risk factors in the development of cardiovascular disease (CVD). Binge drinking is highly prevalent in young adults with a recent rise among women. However, the effects of binge drinking are understudied in women compared to men. My preliminary data show that young women who had a history of repeated binge drinking displayed a greater increase in SBP and a greater decrease in arterial function compared with young men. In addition, these adverse vascular changes in women, but not men, were associated with higher 24-hr urinary levels of norepinephrine (NE), a vasoconstrictor and marker of sympathetic activity. I postulated that the increased sympathetic vasoconstriction associated with binge drinking in women would adversely affect ambulatory SBP. Therefore, this study aims to address my hypothesis that compared with men, the adverse effect of binge drinking on ambulatory blood pressure and arterial function are more pronounced in women due to increased sympathetic vasoconstriction. To this end, I will take primary leadership and use an integrated approach with both clinical in vivo (Aim 1) and mechanistic ex vivo (Aim 2) models in young adults (18-35 years). In Aim 1, I will investigate sex differences in the effect of repeated binge drinking on ambulatory blood pressure, arterial function and sympathetic vasoconstriction. In Aim 2, I developed a novel ex vivo model to simulate one-time binge drinking in isolated human resistance arterioles, the major regulatory site of blood pressure. I will use this model to determine if NE contributes to sex differences in the effect of one-time binge drinking on arterial function. My clinical and mechanistic data will build the foundation for developing an intervention focusing on blood pressure and arterial function to prevent alcohol-induced hypertension and CVD in women. This study is significant and will ultimately improve our ability to reduce the CVD burdens in women. For the applicant, this application will facilitate a timely transition to independence.
|Program type||Postdoctoral Fellowship|
|Effective start/end date||01/01/2020 → 12/31/2021|