The purpose of the proposed research is to address the question of whether the aging process alters vascular responsiveness to vasoconstrictor or vasodilator agents. Initially the responsiveness to alpha- and beta-adrenergic drugs will be examined, followed by nitrovasodilators. Previous work has shown that beta receptor sensitivity is decreased with aging, while results with alpha receptor mediated drugs is inconsistent. Interpretation of these earlier studies is often complicated by the presence of reflex homeostatic responses to the systemic administration of drugs. This proposal will utilize a technique for measuring dorsal hand vein compliance which is reproducible and allows local responses to be measured without systemic effects. Preliminary experiments have demonstrated the feasibility of the approach. A cross-sectional study of 30 subjects between the ages of 20-80 will be carried out. Individual dose-response curves will be generated for a variety of clinically-important vasoactive compounds used in the treatment of hypertension, angina and other vascular disorders. Data will be analyzed by appropriate pharmacological models and various classes of vasodilators or vasoconstrictors will be investigated to look for age-dependent changes. The hand vein compliance technique is a potentially powerful method for identifying differences in responsiveness among subgroups of patients (i.e. hypertensives) for studying combinations of drugs (and thus understanding their possible mechanism of action) and for investigating the phenomenon of changes in effector organ sensitivity with time. Clinically, this information may contribute to more optimal use of vasoactive drugs in the aging population.
