While the arterial side of the circulation has been extensively studied in older and hypertensive humans, much less is known about the venous system. Venous hemodynamic function declines with age and has been implicated in the pathophysiology of hypertension. Animal models provide evidence that venous hemodynamic function is altered in the development and established phases of hypertension, yet data are lacking in humans. This is relevant considering the prevalence of hypertension is estimated to be 50 million, and older Americans are disproportionately affected. Thus, this proposal will provide insight into the mechanisms underlying age- and disease-related alterations in venous compliance. Structural changes in the walls of the veins are expected to dominate the age-related differences in venous compliance (similar to what occurs on the arterial side of the circulation), but alterations in venous smooth muscle tone and responsiveness are hypothesized to underlie the disease-related differences. In order to accomplish these aims, a cross sectional study design will be employed, utilizing four distinct groups: young normotensive, young hypertensive, older normotensive, and older hypertensive adults (factorial study design). A recently validated noninvasive approach (Halliwill et al) will be utilized. Individual forearm and leg pressure-volume relationships will be plotted and modeled using a quadratic regression to generate compliance curves. Curves will be generated under basal conditions, following sublingual nitroglycerin administration and during ischemic handgrip exercise (restricted randomization), to examine the effect of smooth muscle relaxation and sympathetically mediated contraction, respectively, on venous compliance. The findings from these studies will significantly advance our understanding of venous function in older normotensive and hypertensive adults, possibly leading to innovative therapeutic approaches for the treatment of hypertension. Funding of this R03 proposal will allow the P.I. to submit a subsequent R01 focused on one of the following aging-related areas: (1) the role of venous hemodynamic function in the development of hypertension, (2) the effects of a longitudinal endurance exercise training program on venous hemodynamic function, (3) and the potential pathologic effects of the vaso/venoconstrictor endothelin-1 on venous hemodynamic function in older adults.
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