UWY COBRE: NEUROPEPTIDE SIGNALING IN CONTROL OF SALT INTAKE & BLOOD PRESSURE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。本研究旨在研究控制盐摄入量和心血管功能的大脑机制。脑速激肽P物质(SP)和神经激肽B(NKB)参与了高血压的发病机制。为了进一步研究SP和NKB在心血管信号转导中的作用，我们用免疫组织化学方法观察了血压升高后孤束核中SP受体(NK1)和NKB(NK3)受体的内在化。对照组动物NK1和NK3受体免疫组织化学染色显示，胞浆沿细胞膜分布。压力感受器的激活伴随着NST神经元细小珠状树突的出现。这种现象归因于SP的释放和NK1受体的内化。此外，我们还发现，压力感受器的激活导致NK3受体在NST内化。外源性注射NK3受体激动剂可降低压力反射的增益，这是由于抑制了副交感神经介导的心动过缓。总的来说，这些结果显示了两种速激肽在控制血压中的功能作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The present studies are directed at studying the brain mechanisms controlling salt intake and cardiovascular function. The brain tachykinins, substance P (SP) and neurokinin B (NKB), are implicated in the pathogenic mechanisms underlying hypertension. To further investigate the functions of SP and NKB in cardiovascular signaling, we visualized, using immunohistochemistry, the internalization of SP receptors (NK1) and NKB (NK3) receptors in the nucleus of the solitary tract following increases in blood pressure. In control animals, NK1 and NK3 receptor immunohistochemistry revealed that the recepotrs were distributed along the plasma membrane. Activation of baroreceptors was accompanied by the appearance of finely-beaded dendrites of NST neurons. This appearance is attributed to the release of SP and the internalization of the NK1 receptor. In addition, we show that activation of baroafferents results in the internalization of NK3 receptors in the NST. Exogenous injection of NK3 receptor agonists decreased the gain of the baroreflex, which was due to a suppression of parasympathetic mediated bradycardia. Collectively, these results show a functional role of two tachykinin peptides in the control of blood pressure.