REGULATION OF MUSCLE BLOOD FLOW IN OLD AGE

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The goal of this application is to test the hypothesis that human aging alters the regulation of blood flow to active skeletal Skeletal muscles during whole body exercise. Compelling evidence supporting this hypothesis comes from our recent finding that leg blood flow during submaximal cycle ergometry is reduced in older versus younger aerobically-trained men, despite similar cardiac output and leg muscle mass. To determine if reduced skeletal muscle perfusion duration exertion is an inevitable consequence of aging, and to clarify the mechanisms involved, we will address the following specific aims: 1) Is active muscle blood flow during exercise influenced by age, gender, or chronic physical activity? 2) Does an acute reduction in the work of breathing (inspired HeO2) during submaximal exercise augment active muscle blood flow to a greater extent in older compared to younger subjects and if so, how? 3) Is there evidence for an age-associated increase in sympathetic vasoconstriction in active skeletal muscle during exercise and if so, is this related to differences in muscle fiber type (needle biopsy)? 4) Does an aerobic exercise training program modify the effects of age on exercise hyperemia and vasodilator responsiveness in the leg? These questions will be investigated by measuring leg blood flow (femoral vein thermodilution), leg norepinephrine spillover, arterial pressure, and cardiac output (acetylene uptake) during graded leg cycle ergometry in healthy younger z920-30 years) and older (60-75 years) men and women. Leg muscle mass (DEXA) and leg vasodilator responses to local administration of prazosin (Aim 3) and endothelial-dependent and independent agonists (ACh, NTP, papavarine, Aim 4) will also be assessed as a function of age. We hypothesize that normal aging is associated with reduced active muscle vasodilation during dynamic exercise and that this is due to increased respiratory muscle blood flow demands, augmented sympathetic vasoconstriction in the legs, and impaired respiratory muscle blood flow demands, augmented sympathetic vasoconstriction in the legs, and impaired endothelium-dependent vasodilation. These investigations should contribute significantly to our understanding of the decline in physical functional capacity and increased incidence of chronic disease in older humans.