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: 7653338
• 负责人: Cheryl M Heesch
• 金额: $ 45.17万
• 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/7653338
• 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; public health relevance; 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可维持血容量升高，并且交感神经流出的动脉压力感受反射控制可用于预防高血压，但代价是对低血压刺激的代偿反应（尽管心脏和脉管系统的基线交感张力轻度升高）。妊娠期严重高血压疾病的一个标志是缺乏这些适应和过度的交感神经兴奋。 P.I. 实验室研究的长期目标是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。当前项目的目的是确定： 1.) 怀孕是否与包含交感神经投射神经元的大脑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上的抑制性神经递质 GABA 的调节在怀孕和非怀孕大鼠之间是否不同； 3.) 黄体酮的神经活性类固醇代谢物 31-OH、DHP 是否会导致包含前交感神经元的不同大脑区域中 GABA 能抑制的明显差异。所提出的实验的一个优势是参与研究人员的不同专业知识，这允许在整个动物、细胞群、单细胞和分子水平上采用多层次的方法。妊娠和分娩期间的出血和高血压疾病对孕产妇死亡率（约占死亡的 30%）和发病率有显着影响。因此，这些实验的结果对国民健康具有重要意义。公共卫生相关性：在发达国家，出血和高血压疾病约占孕产妇死亡的 30%，而在欠发达国家，这一比例甚至更高。控制血管收缩神经活动的主要适应发生在正常妊娠期间，虽然通常有益于胎儿和产妇健康，但会导致对直立性和出血性低血压的易感性增加。严重的妊娠高血压疾病的特征是血管收缩活性过度。本申请中提出的实验旨在确定妊娠诱导的中枢神经系统控制血管收缩神经的适应机制，并且与妊娠和分娩期间的孕产妇健康高度相关。