Vascular reactivity to compounding stressors across the blood alcohol curve: Interactions with chronic drinking and an isometric handgrip challenge

This dissertation examined how alcohol intoxication dynamically alters cardiovascular regulation, as well as how these effects are modulated by transient physical stressors and binge drinking frequency. Ninety-two healthy young adults (aged 21-29) classified as either binge drinkers (n=46) or non-binge drinkers (n=46) completed a within-subjects alcohol administration study. Participants received either placebo (n=40) or alcohol (0.4 g/kg ethanol; n=52), with most completing seven intermittent isometric handgrip tasks across the intoxication time course to impose controlled sympathetic activation. A subset receiving alcohol completed no handgrip tasks (n=12) to isolate alcohol's cardiovascular effects. Continuous blood pressure was monitored throughout the session and analyzed using mixed-effects models to characterize dynamic trajectories across intoxication phases and examine how transient sympathetic challenges interacted with phase-dependent alcohol effects.Results demonstrated that alcohol produced nonlinear blood pressure trajectories consistent with its pharmacological profile, with substantial individual heterogeneity driven by metabolic variation in absorption and elimination rates. During the handgrip tasks, alcohol interacted with sympathetic activation to reshape cardiovascular regulation over time, with early intoxication amplifying cardiovascular responses to grip contraction while later effects attenuated as fatigue accumulated. Alcohol also altered the coupling between blood pressure and grip force production, sustaining this relationship across the session compared to progressive decoupling observed in the placebo condition. Post-exercise recovery exhibited an oscillatory pattern, with alcohol facilitating faster recovery near peak blood alcohol concentration. Contrary to predictions, binge and non-binge drinkers exhibited similar blood pressure trajectories during intoxication outside of the handgrip tasks. However, under the combined challenge of alcohol and handgrip tasks, binge drinkers showed elevated overall blood pressure, exaggerated cardiovascular reactivity during rapid demand-recovery transitions, and blunted responsiveness to alcohol's effects on post-exercise recovery.These findings reveal that alcohol's cardiovascular effects are dynamic and context-dependent, emerging most clearly when physiological systems are challenged rather than at rest. The detection of early cardiovascular dysregulation in young binge drinkers specifically under layered stressors provides preliminary evidence of allostatic load and highlights the utility of layered challenge paradigms for identifying subclinical risk. This work broadly demonstrates that alcohol-related cardiovascular risk cannot be fully understood using static measures alone but also requires approaches that evaluate systemic adaptation to physiological load, offering insight into mechanisms that may ultimately link acute intoxication patterns to long-term health outcomes.