The purpose of the proposed research is to identify mechanisms underlying hormonal and neural efferent modulation of aortic baroreceptors (BRs). These mechanisms are important to our understanding of neurocirculatory control, since changes in BR discharge characteristics may alter baroreflex function whenever vasoactive hormones and/or sympathetic drive are enhanced. Local mechanisms acting on the BR endings are difficult to resolve using intact or in situ preparations due to concurrent changes in systemic hemodynamics. The proposed project will employ an in vitro preparation that will enable the chemical, mechanical, and neural stimuli to the BRs to be precisely controlled. The preparation will consist of the rabbit aortic arch and associated aortic afferent and sympathetic efferent innervation. Responses of single-unit BRs will be recorded simultaneously with arch pressure, diameter, and wall thickness, and from these measurements BR discharge will be related to vascular stress and strain. The first study will resolve whether previously reported excitatory and inhibitory effects of efferent nerve stimulation on myelinated aortic BRs are a result of concentration-dependent effects of the neurotransmitter norepinephrine on the BR and smooth muscle cells, and whether similar effects are produced in unmyelinated fibers. This will involve comparing arch and BR dose-response curves from efferent nerve stimulation at increasing frequencies with curves from application of exogenous norepinephrine at increasing concentrations (in the same fiber). Responses to efferent stimulation also will be examined when uptake and enzymatic degradation of norepinephrine are blocked pharmacologically to raise intramural norepinephrine concentrations. The second aim will be to determine the effects of selected vasoactive hormones on BR static discharge properties. These substances include arginine vasopressin, angiotensin II, atrial naturetic factor, and substance P, all of which are implicated in cardiovascular homeostasis. The focus will be on discriminating between direct chemical effects on the BR endings and effects due to local smooth muscle contraction or relaxation. Effects on myelinated and unmyelinated BRs will be compared. The third aim will be to determine smooth muscle effects on BR dynamic discharge properties. This will involve applying step, sinusoidal, and pink noise pressure inputs in untreated and in constricted and relaxed arches. The fourth aim will be to examine the smooth muscle effects on BR discharge over nonlinear regions of the arch and BR pressure-response curves, and to compare autoactive BRs, which fire spontaneously below pressure threshold, with the more typical quiescent BRs, which are silent below threshold. There may be inherent differences in these units and their response to vasoconstriction. The fifth aim will be to establish whether aortic BRs respond to changes in blood flow and whether their response is mediated by the endothelium, which may release vasoactive substances or substances that act on the BR endings.