BARORECEPTOR/HORMONAL INTERACTIONS

压力感受器/荷尔蒙相互作用

• 批准号: 2220912
• 负责人: MARIANA MORRIS
• 金额: $ 15.73万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2220912
• 关键词: angiotensin II; antisense nucleic acid; autonomic ganglion; baroreceptors; brain stem; cardiovascular function; denervation; gene expression; histology; hormone regulation /control mechanism; in situ hybridization; laboratory rat; medulla oblongata; messenger RNA; neural transmission; neurophysiology; oxytocin; paraventricular nucleus; peptide hormone; salt intake; vasopressins

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.

主脑脑轴轴是自主和 内分泌功能。我们假设催产素，一种肽素 在此途径中的发射器调节心血管反应，并 这是通过钠强调的。此外，我们建议中央催产素 可能是重要的未欣赏的神经内分泌调节剂 心血管和水力学平衡。初始的关键发现 赠款期是通过 压力受体神经支配会导致下丘脑的慢性变化 神经分泌细胞，使其对钠的作用过敏。 催产素系统在mRNA表达方面的反应增加 鉴于假设的肽分泌特别有趣 催产素作为心血管控制与盐之间的联系 平衡。提出了一项研究计划来研究肽能 PVN与脑干之间的相互作用，脑干的影响 催产素在心血管和交感神经功能上，影响 催产素mRNA表达的压力感受器输入和中央刺激 催产素在压力受体诱导的盐摄入变化中的作用。 该提案将采用技术允许评估的技术 中央神经元功能，肽mRNA表达，肽分泌和 生理反应。微透析将用于测量中央 和全身催产素释放，研究 心血管和同情反应以及原位杂交方法 用于评估细胞mRNA水平的变化。具体 该提案的目的是：1）通过 检查PVN刺激对脑干催产素释放的影响和 心血管参数2）检查催产毒素能的作用 脑干途径通往髓质的背迷走神经复合体 自主流出和心血管功能的调节3）评估 肽mRNA对压力受体神经（时间过程）的反应， 高渗盐水和血管紧张素以及4）确定中心的作用 盐摄入盐的催产素介导的变化。