BARORECEPTOR/HORMONAL INTERACTIONS

室旁-脑干轴作为自主神经和神经元的整合者， 内分泌功能我们假设催产素，一种肽能物质 在这一途径中的递质，调节心血管反应， 这是由钠加剧。此外，我们认为，中枢催产素 可能是一种重要的未被重视的神经内分泌调节剂， 心血管和水矿物质平衡。最初的一个关键发现是， 授予期是PVN-脑干回路中断， 压力感受器去神经支配引起下丘脑慢性变化 神经分泌细胞，使它们对钠的作用过敏。 催产素系统在mRNA表达方面的反应增加 和肽分泌是特别有趣的，鉴于假设的 催产素作为心血管控制和盐之间联系的作用 平衡提出了一个研究方案， PVN与脑干的相互作用，脑干对PVN的影响， 催产素对心血管和交感神经功能的影响 压力感受器输入和中枢刺激对催产素mRNA表达的影响 以及催产素在压力感受器引起的盐摄入变化中的作用。 该提案将采用的技术，将允许评估 中枢神经功能、肽mRNA表达、肽分泌和 生理反应。微透析将用于测量中心 和全身催产素释放，显微注射的研究， 心血管和交感神经反应和原位杂交方法 用于评价细胞mRNA水平的变化。具体 该提案的目的是：1）研究PVN-脑干相互作用， 检查PVN刺激对脑干催产素释放的影响， 心血管参数2）检查催产素能的作用 脑干通路的背迷走神经复合体的延髓 自主神经流出和心血管功能的调节3）评估 肽mRNA对压力感受器去神经支配的反应（时程）， 高渗盐水和血管紧张素和4）确定中枢神经系统的作用 催产素在压力感受器介导的盐摄入量的变化。

The paraventricular-brainstem axis acts as an integrator of autonomic and endocrine function. We hypothesize that oxytocin, a peptidergic transmitter in this pathway, modulates cardiovascular responses and that this is accentuated by sodium. Further we suggest that central oxytocin may be an important an unappreciated neuroendocrine modulator of cardiovascular and hydromineral balance. A key finding in the initial grant period was that interruption of this PVN-brainstem circuit via baroreceptor denervation produces chronic changes in the hypothalamic neurosecretory cells, making them hypersensitive to the effects of sodium. The increased response of the oxytocin system in terms of mRNA expression and peptide secretion is especially intriguing in view of the postulated role of oxytocin as a link between cardiovascular control and salt balance. A research program is proposed to study the peptidergic interactions between PVN and brainstem, the influence of brainstem oxytocin on cardiovascular and sympathetic nervous function, the influence of baroreceptor input and central stimulation on oxytocin mRNA expression and the role of oxytocin in baroreceptor-induced changes in salt intake. The proposal will employ techniques which will allow for the evaluation of central neuronal function, peptide mRNA expression, peptide secretion and physiological responses. Microdialysis will be used for measuring central and systemic oxytocin release, microinjection for the study of cardiovascular and sympathetic responses and in situ hybridization methods for the evaluating of the changes in cellular mRNA levels. The specific aims of the proposal are: 1) to study PVN-brainstem interactions by examining the effect of PVN stimulation on brainstem oxytocin release and cardiovascular parameters 2) to examine the role of oxytocinergic brainstem pathways to the dorsal vagal complex of the medulla in the regulation of autonomic outflow and cardiovascular function 3) to evaluate the peptide mRNA responses to baroreceptor denervation (time course), hypertonic saline and angiotensin and 4)To determine the role of central oxytocin in baroreceptor-mediated changes in salt intake.