Our long-term goal is to characterize the optimal blood flow pattern for improving vascular endothelial function in humans. Our approach to enhance endothelial dilatory function will utilize the muscle contraction-blood flow interaction during repeated contractions. The resulting oscillatory blood flow pattern places shear stress on the endothelium and may result in injury. The proposed research aims to test the hypotheses that muscle contractions producing blood flow oscillations of the largest amplitude will result in the most injury to the endothelium, and that exercise training at different blood flow patterns will differentially improve endothelial dilatory function. Different blood flow patterns will be generated by varying muscle contraction duty cycle and tension development during repeated dynamic forearm muscle contractions, and endothelial damage will be assessed by measuring plasma concentrations of von Willebrand Factor. Handgrip exercise training will be performed at different blood flow patterns (large flow oscillations vs. large retrograde flow). Endothelial dilatory function will be assessed by measuring peak reactive hyperemia and sublingual administration of nitroglycerin. The proposed research will advance knowledge of how physical activity may improve vascular health, and may lead to the development of an effective exercise intervention aimed at improving endothelial-dependent dilator function in humans. [unreadable] [unreadable] [unreadable]