Little reliable data currently exists to support the prevailing concept that adrenergic control of vascular smooth muscle becomes less effective with age. Therefore, various components of the adrenergic neuroeffector mechanism of vascular smooth muscle will be studied in vivo and in vitro. Young, mature and senescent rats will be studied in order to answer three questions: 1. Does adrenergic nerve function alter with advancing age? Norepinephrine (NE) content and neuronal accumulation of metaraminol will be measured as indices of adrenergic nerve density. The fraction of total endogenous NE content released during nerve stimulation will be determined in vitro, and the effectiveness of pre-synaptic feedback mechanisms evaluated. 2. Does vascular smooth muscle reactivity change with advancing age? Classical pharmacological techniques involving measurement of vascular smooth muscle contraction and relaxation will be used to assess changes in both alpha and beta adrenergic receptors. Smooth muscle responsiveness to adrenergic nerve stimulation will be assessed in vitro, and the role of the endothelium in smooth muscle relaxation evaluated. 3. Can these functional changes be demonstrated in vivo? Turnover of NE will be evaluated in vivo using a steady state technique. Elucidation of possible age-related alterations in adrenergic control of vascular smooth muscle is vital to understanding how cardiovascular homeostasis is maintained in elderly individuals as well as to designing appropriate therapy for a host of cardiovascular diseases.
