Catecholaminergic (CA) systems, whether in the brain or the periphery, seem to possess a dynamic capacity to alter synthesis, release, and postsynaptic responsiveness, and thus to maintain a relatively constant state of synaptic activity even in the face of changing demands. Such plasticity may underlie the common observation that damage to CA systems rarely results in severe disturbances of physiology or behavior. Indeed, experiments in the central nervous system have addressed just this issue but progress has been impeded by difficulties in quantifying activity within central CA pathways, and by an inadequate understanding of their functional role. In an attempt to relate more directly the compensatory neurochemical changes after neural damage to restoration of function, the research proposed here will examine the sympathoadrenal regulation of cardiovascular function as a model of central CA systems, and will study its response to subtotal sympathectomy. Specifically, we will focus on the following issues: (1) A characterization of the initial deficits in, and subsequent recovery of, cardiovascular function after subtotal sympathectomy. Thus, we will determine pressor responses and heart rate increments after preganglionic stimulation in pithed rats treated with systemic 6-HDA or its vehicle 3 days, 1 week, 3 weeks, or 6 weeks previously. We also will measure chronotropic responses in isolated atria and contractile responses in isolated perfused mesenteries obtained from animals similarly treated. (2) A detailed analysis of the neurochemical changes within the undamaged elements of the sympathoadrenal system which lessen the severity of the initial deficits and permit recovery of function to occur prior to complete regeneration of the nerves. This analysis will focus on the ability of residual sympathetic nerves, as well as the adrenal medulla, to increase their synthesis and release of CAs, and whether this CA has a greater influence on denervated target tissues such as the heart and vasculature. This combined approach of in vivo and in vitro techniques should permit a complete and precise profile of the mechanisms responsible for recovery of function in a damaged neuronal system.
