The long-term goal of this research program is to determine the central pathways that regulate vasopressin release in order to understand how their dysfunction might contribute to pathophysiology. The regulation of vasopressin release may be of particular importance in understanding dilutional hyponatremia, a common hydromineral imbalance that increases the morbidity and mortality of patients with congestive heart failure. Normally, vasopressin release is transiently inhibited by water intake, and the failure of water intake to suppress circulating vasopressin could contribute to dilutional hyponatremia. The central nervous system mechanisms that mediate the inhibition of vasopressin by water intake are not known. Purpose: Previous studies indicate that afferents from the oropharyngeal cavity and the gastrointestinal system inhibit vasopressin release associated with water intake. The goal of this proposal is to define the role of oropharyngeal factors in the neural network that influences the release of vasopressin and oxytocin following water intake.
Specific Aims : 1. To determine the contribution of gustatory and oropharyngeal afferents in the inhibition of vasopressin release by water intake. Hypothesis: The inhibition of vasopressin release by water intake involves oropharyngeal afferents from the IXth and Xth cranial nerves but not gustatory afferents of the Vllth cranial nerve. 2. Experiments will evaluate the contribution of the nucleus of the solitary tract (NTS) in the inhibition of vasopressin neurons in the rat supraoptic nucleus (SON) by water intake. Hypothesis: The inhibitory effects of water intake on SON neurons are mediated through NTS neurons that project to the parabrachial nucleus. 3. Test the role of the parabrachial nucleus (PBN) in the inhibition of vasopressin release by water intake. Hypothesis: The PBN is required for water intake to inhibit vasopressin release. 4. Test the role of the perinuclear zone (PNZ) of the SON in the inhibition of vasopressin neurons associated with water intake. Hypothesis: The PBN acts on the SON through the PNZ to inhibit vasopressin release following water intake. Methods: The studies will employ in vivo single unit electrophysiological recording with juxtacellular labeling, c-Fos immunocytochemistry in combination with retrograde track tracing and in situ hybridization histochemistry, and lesion studies with measurements of plasma vasopressin and oxytocin to test these hypotheses. Benefits: The results will provide new information regarding the control of vasopressin secretion and how these systems contribute to pathophysiology. ? ? ?
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