(Verbatim from the application): Vasopressin is one of the major hormones involved in body fluid homeostasis. It is secreted by neurons located in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. Changes in blood pressure, blood volume and plasma osmolality influence the activity of vasopressin neurons in the SON and PVN by activating specific CNS pathways. The pathways that mediate these effects of vasopressin neurons in the SON have not been fully described. We have previously studied the CNS pathways involved in transmitting information from arterial baroreceptors to the SON of the rat. Much less is known about the CNS pathways involved in the regulation of the activity of SON neurons by cardiac receptors. The experiments described in this proposal will examine the neural pathways that bring arterial baroreceptor information and cardiac receptor information to the SON. First, we will identify the areas in the CNS that are activated by volume expansion with isotonic saline in unanesthetized rats using Fos immunocytochemistry and we will determine the role of cardiac receptors in the activation of these regions. The data resulting from these studies will be used as the basis for in vivo electrophysiological experiments in which we obtain extracellular recordings from vasopressin and oxytocin SON neurons in anesthetized rats. In these studies, we will directly stimulate cardiac receptors to determine their influence on the activity of SON neurons. The role of CNS regions identified in the Fos experiments will be tested for their importance in the electrophysiological responses of SON neurons to cardiac receptor stimulation by lesioning them with an excitotoxin, ibotenic acid. Our preliminary results indicate two important findings. First, there may be considerable overlap between the pathways bringing arterial baroreceptor and cardiac receptor information to the SON. Second, the activation of cardiac receptors may differentially regulate the activity of vasopressin and oxytocin neurons in the SON. Recently, alterations in the non-osmotic regulation of vasopressin release have been linked to high circulating levels of vasopressin in end stage heart failure and to changes in extracellular fluid volume observed during space flight and prolonged bed rest (Norsk, 1996). The control of vasopressin release is also altered during pregnancy. Before we can address how vasopressin release is changed during these states, we need to determine the neural mechanisms that participate in the non-osmotic control of vasopressin secretion. Therefore, understanding the neural pathways involved in the arterial baroreceptor and atrial receptor regulation of vasopressin release is a necessary first step that is needed to address the role of vasopressin in health and disease.
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