Central nervous system plasticity in sympathoinhibition in pregnancy

项目总结： 在正常妊娠中，重新设置容量控制系统可维持较高的血液浓度 容量和动脉压力感受性反射控制交感神经流出适用于保护 抗高血压，代价是对低血压刺激的代偿反应 (尽管心脏和血管系统的基础交感神经张力略有升高)。一个 妊娠期严重高血压疾病的特征是缺乏这些适应 和夸张的共鸣刺激。“S”研究的长远目标 实验室是为了了解卵巢激素对中枢神经系统的影响机制 神经系统对交感神经活动的控制。当前项目的目标是 确定：1.)如果怀孕与抑制输入的不同变化有关 脑内含有交感投射神经元的区域；如果一氧化氮(NO) 抑制性神经递质GABA对交感投射神经元的调制作用 怀孕和未怀孕的大鼠之间存在差异；以及如果神经活性类固醇 孕酮的代谢物，3？-羟基，DHP，有助于在 含有交感前神经元的不同脑区的GABA能抑制。一个 拟议的实验的优势在于参与研究人员的不同专业知识 这允许在整个动物、细胞种群、单个细胞、 和分子水平。妊娠期间的出血和高血压疾病以及 分娩对产妇死亡率(约占死亡人数的30%)和发病率有很大影响。 因此，这些实验的结果对国家健康具有重要影响。

Project Summary: In normal pregnancy resetting of volume control systems maintains elevated blood volume, and arterial baroreflex control of sympathetic outflow is adapted to protect against hypertension, at the expense of compensatory responses to hypotensive stimuli (although baseline sympathetic tone to the heart and vasculature is mildly elevated). A hallmark of serious hypertensive disorders in pregnancy is the lack of these adaptations and exaggerated sympathoexcitation. The long term goal of research in the P.I.'s laboratory is to understand mechanisms for effects of ovarian hormones on central nervous system control of sympathetic nerve activity. Aims of the current project are to determine: 1.) If pregnancy is associated with differential changes in inhibitory inputs to regions of the brain containing sympathetic projection neurons; 2.) if nitric oxide (NO) modulation of the inhibitory neurotransmitter GABA on sympathetic projection neurons differs between pregnant and nonpregnant rats; and 3.) if the neuroactive steroid metabolite of progesterone, 3¿-OH, DHP, contributes to apparent differences in GABAergic inhibition in different brain regions containing presympathetic neurons. A strength of the proposed experiments is the varied expertise of participating investigators which allows for a multilevel approach at the whole animal, cell population, single cell, and molecular level. Hemorrhage and hypertensive disorders during pregnancy and delivery contribute significantly to maternal mortality (~30% of deaths) and morbidity. Thus, results from these experiments have important national health implications.