REGULATION OF MUSCLE BLOOD FLOW IN OLD AGE

The central hypothesis of this proposal is that active skeletal muscle blood flow during large muscle dynamic exercise is reduced as a function of age in humans. Specifically, we hypothesize that leg muscle vasodilation during exercise at any submaximal workload is reduced with advancing age in men and women (vs. younger control subjects) (Specific Aim 1) and that this is due to increasing competition for cardiac output by the aging respiratory muscles (Specific Aim 2), augmented sympathetic vasoconstriction in the active leg muscles (Specific Aim 3), and impaired endothelial-dependent vasodilation (Specific Aim 4). A critical requirement for evaluating these hypotheses is our ability to combine measurements of cardiac output and leg blood flow during large muscle dynamic exercise, with physiological and pharmacological evaluation of vascular responsiveness in the leg.