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

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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.