Neural Regulation of Vasopressin Release

描述(申请人提供)：这项研究计划的长期目标是确定调节加压素释放的中枢通路，以便了解它们的功能障碍如何对病理生理学起作用。对加压素释放的调节可能对了解稀释性低钠血症特别重要，稀释性低钠血症是一种常见的水矿物质失衡，会增加充血性心力衰竭患者的发病率和死亡率。正常情况下，血管加压素的释放会被水摄入暂时抑制，而水摄入不能抑制循环中的血管加压素可能会导致稀释性低钠血症。中枢神经系统调节水摄入抑制加压素的机制尚不清楚。目的：以前的研究表明，来自口咽腔和胃肠道系统的传入抑制了与水摄入相关的加压素的释放。这项建议的目的是确定口咽因素在神经网络中的作用，该因素影响水摄入后血管加压素和催产素的释放。具体目的：1.确定味觉传入和口咽传入在水摄入抑制血管加压素释放中的作用。假设：进食水对加压素释放的抑制涉及来自第X和第X脑神经的口咽传入，而不涉及第V11脑神经的味觉传入。2.实验将评估孤束核(NTS)在饮水抑制大鼠视上核(SON)加压素神经元中的作用。假设：饮水对SON神经元的抑制作用是通过投射到臂旁核的NTS神经元来实现的。3.检测臂旁核(PBN)在水摄入抑制加压素释放中的作用。假设：PBN是水摄取所必需的，以抑制加压素的释放。4.测试SON核周区(PNZ)在抑制与饮水有关的加压素神经元中的作用。假设：PBN通过PNZ作用于SON，抑制水摄入后血管加压素的释放。方法：采用细胞旁标记的在体单单位电生理记录，c-Fos免疫细胞化学结合逆行追踪和原位杂交组织化学，以及测定血浆加压素和催产素的损伤实验来验证这些假说。益处：研究结果将提供有关加压素分泌控制的新信息，以及这些系统如何对病理生理学做出贡献。

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.