Central nervous system plasticity in sympathoinhibition in pregnancy

项目摘要： 在正常妊娠中，容量控制系统的重新设置维持了升高的血流量。 交感神经流出的动脉压力反射控制适于保护 对抗高血压，代价是对过度刺激的代偿反应 （尽管心脏和脉管系统的基线交感神经紧张轻度升高）。一 妊娠期严重高血压疾病的标志是缺乏这些适应性 和过度的交感神经兴奋P.I.研究的长期目标。的 实验室的目的是了解卵巢激素对中枢神经系统的影响机制， 交感神经活动的神经系统控制。本项目的目标是 确定：1.）如果怀孕与抑制性输入的差异变化有关， 含有交感神经投射神经元的脑区域; 2.）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节 怀孕和非怀孕大鼠之间的差异;和3.）如果神经活性类固醇 孕酮的代谢产物3 <$-OH，DHP，导致了 含有前交感神经元的不同脑区的GABA能抑制。一 所提议的实验的优势在于参与研究的研究人员的各种专业知识 其允许在整个动物、细胞群体、单个细胞 分子水平。妊娠期出血和高血压疾病， 分娩在很大程度上导致孕产妇死亡（约占死亡人数的30%）和发病率。 因此，这些实验的结果具有重要的国家健康意义。

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.