PROJECT SUMMARY/ABSTRACT Cardiovascular disease (CVD) is the leading cause of death in the developed world. As age is a major risk factor for CVD and the average lifespan of humans is increasing, CVD is projected to reach unprecedented levels and place an enormous burden on the healthcare system. While these demographic shifts are inevitable, the development of CVD is preventable. As high blood pressure accounts for more CVD deaths than any other modifiable risk factor, interventions aimed at the management of blood pressure are crucial in preventing these sobering CVD projections from becoming reality. Heat therapy, in the form of hot bath and sauna, is an ancient practice that has recently gained attention in the treatment and prevention of CVD as regular sauna use is associated with a reduced risk of all-cause CVD deaths. Like exercise, many of the chronic benefits of heat therapy are likely mediated during the recovery period. For example, a single bout of exercise promotes a sustained reduction in blood pressure, termed post-exercise hypotension, which transiently lowers elevated blood pressure into normotensive ranges and potentiates beneficial cardiovascular adaptation with exercise training. Similarly, we and others have demonstrated a sustained reduction in blood pressure following a single bout of heat stress in both healthy and patient populations. However, the neurovascular mechanisms which underlie this post-heating hypotensive window of opportunity are unknown, representing a critical gap in knowledge. Therefore, we aim to explore post-heating hypotension, baroreflex control, and sympathetic vascular transduction in young and aged humans following whole-body heat stress. We hypothesize that post-heating hypotension is supported by downward and leftward baroreflex resetting in the absence of altered sympathetic vascular transduction in both young and aged adults. Additionally, we hypothesize that the magnitude of this blood pressure reduction and baroreflex resetting is exaggerated among aged adults. Overall, this work improves our understanding of the adaptive role of heat stress and advances heat therapy as a therapeutic option for the management of blood pressure and prevention of CVD. As the candidate, Ms. Larson completes the proposed research at the University of Oregon alongside her experienced co-mentors, Drs. Minson and Halliwill, she will gain clinical trial research experience, learn “gold-standard” technical laboratory skills, and continue to develop as an effective science communicator, educator, and mentor. As such, the proposed project will serve as an essential installment toward Ms. Larson’s larger career goal to obtain a post- doctoral research position and eventual faculty position at a major research university.