Neural Regulation of Vasopressin Release

描述（由申请人提供）：本研究项目的长期目标是确定调节抗利尿激素释放的中枢通路，以了解其功能障碍如何影响病理生理。抗利尿激素释放的调节可能对理解稀释性低钠血症特别重要，低钠血症是一种常见的水矿物质失衡，增加充血性心力衰竭患者的发病率和死亡率。正常情况下，抗利尿激素的释放会被水的摄入短暂地抑制，而水的摄入不能抑制循环抗利尿激素可能会导致稀释性低钠血症。中枢神经系统通过饮水介导抗利尿激素抑制的机制尚不清楚。目的：先前的研究表明，口咽腔和胃肠道系统的传入信号抑制与水摄入相关的抗利尿激素释放。本提案的目的是确定口咽因素在神经网络中的作用，影响水摄入后抗利尿激素和催产素的释放。具体目标：1；确定味觉和口咽传入神经在水摄入抑制抗利尿激素释放中的作用。假设：水摄入对抗利尿激素释放的抑制作用涉及来自第8和第6脑神经的口咽传入神经，但不涉及第5脑神经的味觉传入神经。2. 实验将评估孤立束核（NTS）在饮水对大鼠视上核（SON）抗利尿激素神经元的抑制中的作用。假设：水摄入对SON神经元的抑制作用是通过投射到臂旁核的NTS神经元介导的。3. 测试臂旁核（PBN）在水摄入抑制抗利尿激素释放中的作用。假设：PBN是水摄入抑制抗利尿激素释放所必需的。4. 测试SON的核周区（PNZ）在抑制与水摄入相关的加压素神经元中的作用。假设：PBN通过PNZ作用于SON，抑制水摄入后抗利尿激素的释放。方法：研究将采用细胞旁标记的体内单单元电生理记录，c-Fos免疫细胞化学结合逆行轨迹追踪和原位杂交组织化学，以及测量血浆加压素和催产素的病变研究来验证这些假设。益处：该结果将提供关于抗利尿激素分泌控制以及这些系统如何参与病理生理的新信息。

DESCRIPTION (provided by applicant): 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.