Physical activity has long been associated with lower morbidity and mortality from heart disease owing to improvements in aerobic capacity and vascular endothelial nitric oxide (NO) bioavailability. While much less is known about the effects of resistance exercise on NO bioavailability recent epidemiological evidence indicate that weight training is correlated with a reduction in cardiac events similar to aerobic exercise. However, the benefits of resistance exercise are complicated by the fact that acute hypertension during weight lifting may be detrimental to endothelial function. Therefore, the overall goal of this proposal is to determine whether chronic resistance training is beneficial or detrimental to endothelial function and NO bioavailibility. The hypothesis is that acute hypertension during resistance exercise impairs arterial and arteriolar endothelial function in non-conditioned sedentary patients by increasing reactive oxygen species (ROS) generation and reducing available nitric oxide (NO). This proposal will test the following hypotheses 1) exertions I hypertension produces a greater increase in ROS and inflammatory mediators in sedentary subjects than in aerobic or resistance trained athletes;and 2) the mechanism of reduced endothelial function in sedentary subjects following weightlifting involves an increase in ROS generation. The results of these studies will impact the mode and intensity of specific exercise recommendations given to patients at risk for cardiovascular disease. This research proposal coupled with the career development program integrates the strengths of the applicant in fundamental vascular biology with assessment human vascular health. The candidate Dr. Shane Phillips is transitioning from a research training position to that of a faculty member at the Medical College of Wisconsin. His career goal is to become an independent translational investigator in the field of human vascular biology and this proposal will provide a supportive research environment as well as institutional support for this transition. The career development plan utilizes state of the art vascular techniques and didactic training geared toward the investigation of clinically relevant questions while building on his previous clinical training in physical therapy and doctoral training in vascular biology. Dr. David Gutterman, an established translational researcher, will provide mentorship during the initial stages of the candidates'independent research career.
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