Central nervous system plasticity in sympathoinhibition in pregnancy

妊娠交感神经抑制中的中枢神经系统可塑性

• 批准号: 8051535
• 负责人: Cheryl M Heesch
• 金额: $ 44.12万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8051535
• 关键词: Accounting; Animals; Antihypertensive Agents; Attenuated; Baroreflex; Blood Circulation; Blood Pressure; Blood Volume; Brain Stem; Brain region; Cardiopulmonary; Cells; Cessation of life; Data; Dendrites; Developed Countries; Developing Countries; Disease; Eclampsia; Event; Female; Fetus; GABA Modulators; Goals; Health; Heart; Heart Rate; Hemorrhage; Hypertension; Hypertension induced by pregnancy; Hypotension; Hypothalamic structure; Laboratories; Maintenance; Maternal Health; Maternal Mortality; Mediating; Metabolism; Microinjections; Molecular; Morbidity - disease rate; Mothers; Nerve; Nervous System Physiology; Neuraxis; Neuromodulator; Neurons; Neurotransmitters; Nitric Oxide; Nitric Oxide Synthase Type I; Ovarian hormone; Physiological; Population; Pre-Eclampsia; Predictive Factor; Predisposition; Pregnancy; Pressoreceptors; Progesterone; Rattus; Reporting; Research; Research Personnel; Risk; Stimulus; Sympathetic Nervous System; Synapses; System; Testing; Vasoconstrictor Agents; design; fetal; gamma-Aminobutyric Acid; mortality; neuronal cell body; neurosteroids; paraventricular nucleus; pregnancy disorder; pregnant; receptor; regional difference; research study; response

DESCRIPTION (provided by applicant): 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, 31-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. PUBLIC HEALTH RELEVANCE: Hemorrhage and hypertensive disorders account for ~ 30% of maternal deaths in developed countries and this percentage is even greater in less developed countries. Major adaptations in control of vasoconstrictor nerve activity occur in normal pregnancy and, although generally beneficial for fetal and maternal health, result in increased susceptibility to orthostatic and hemorrhagic hypotension. Serious hypertensive disorders of pregnancy are characterized by exaggerated vasoconstrictor activity. Experiments proposed in this application are designed to determine mechanisms for pregnancy-induced adaptations in central nervous system control of vasoconstrictor nerves and are highly relevant to maternal health during pregnancy and delivery.

描述（由申请人提供）：在正常妊娠中，容量控制系统的重置维持了血容量的升高，并且以牺牲对低血压刺激的代偿反应为代价，调整了对交感神经流出的动脉压反射控制，以防止高血压（尽管心脏和脉管系统的基线交感神经张力轻度升高）。妊娠期严重高血压疾病的一个特点是缺乏这些适应和过度的交感神经兴奋。P.I.研究的长期目标她的实验室是为了了解卵巢激素对中枢神经系统控制交感神经活动的影响机制。当前项目的目标是确定：1.)如果怀孕与大脑中含有交感投射神经元的区域的抑制性输入的差异变化有关；2)一氧化氮（NO）对交感神经投射神经元抑制性神经递质GABA的调节在怀孕和未怀孕大鼠之间是否存在差异；3)孕酮的神经活性类固醇代谢物31-OH和DHP是否在含有前交感神经元的不同脑区中导致gaba能抑制的明显差异。拟议实验的一个优势是参与研究者的不同专业知识，允许在整个动物，细胞群体，单细胞和分子水平上进行多层次的方法。妊娠和分娩期间的出血和高血压疾病是孕产妇死亡率（约占死亡人数的30%）和发病率的重要原因。因此，这些实验的结果具有重要的国家健康意义。公共卫生相关性：出血和高血压疾病占发达国家孕产妇死亡的约30%，这一比例在欠发达国家甚至更高。血管收缩神经活动控制的主要适应发生在正常妊娠期间，虽然通常有益于胎儿和孕产妇的健康，但会导致体位性和出血性低血压的易感性增加。妊娠期严重高血压疾病的特点是血管收缩活性过高。本应用中提出的实验旨在确定中枢神经系统控制血管收缩神经的妊娠诱导适应机制，并与妊娠和分娩期间的孕产妇健康高度相关。