OVARIAN HORMONE METABOLITES & NEURAL CIRCULATORY CONTROL

卵巢激素代谢物

• 批准号: 2857780
• 负责人: Cheryl M Heesch
• 金额: $ 15.98万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2857780
• 关键词: GABA receptor; angiotensin II; baroreceptors; brain stem; electrophysiology; female; finasteride; fos protein; hemodynamics; homeostasis; hormone regulation /control mechanism; laboratory rat; medulla oblongata; muscimol; neural inhibition; neural transmission; neurochemistry; neuroendocrine system; neuroregulation; pregnancy circulation; progesterone; steroid hormone metabolism; sympathetic nervous system; vasodilation

DESCRIPTION: (Adapted from the application) Normal pregnancy is associated with a 40% increase in blood volume and cardiac output, slight tachycardia, and a decrease in arterial blood pressure. Enhanced baroreflex sympathoinhibition and attenuated sympathoexcitation have been reported in pregnant animals, although the mechanisms have not been well defined. The primary metabolite of progesterone, 3-alpha-hydroxy-dihydroprogesterone (3-alpha-OH-DHP), which is elevated in pregnancy, is a potent positive modulator of central nervous system (CNS) inhibitory GABA-A receptors. Exogenous administration of 3-alpha-OH-DHP to virgin animals mimics the effects of pregnancy: sympathoinhibition is enhanced and sympathoexcitation is attenuated, most likely through a CNS mechanism. Importantly, blocking the formation of endogenous 3-alpha-OH-DHP in pregnant reverses the attenuated sympathoinhibition. Previous studies focused mainly on enhanced arterial baroreflex sympathoinhibition. In the current proposal, experiments are designed to evaluate mechanisms for the attenuation of sympathoexcitatory responses (likely not arterial baroreflex mediated). The general hypothesis is to be tested that attenuated sympathoexcitation during pregnancy is associated with GABAergic mechanisms in central nervous system sites involved in regulation of cardiovascular function. Three possibilities will be evaluated: Increased inhibitory influences from peripheral receptors other than arterial baroreceptors, increased inhibitory influences from the CNS, and decreased excitatory effects in the rostral ventrolateral medulla (RVLM, brainstem site of cardiovascular sympathetic premotor neurons). Experiments in virgin and pregnant rats will evaluate the CNS expression of Fos protein in identified neuronal populations involved in central cardiovascular control following manipulations which normally increase or decrease efferent sympathetic nerve activity. Efferent sympathetic nerve activity will be recorded in other experiments in which inhibitory afferent inputs, CNS inhibitory influences, and excitatory inputs to the RVLM will be altered. Understanding the mechanism for suppressed sympathoexcitatory responses in normal pregnant animals will have important implications for hypertensive disorders or pregnancy which are associated with exaggerated sympathoexcitatory responses.

描述：（改编自应用程序）正常怀孕与 血容量和心输出量增加40%，轻微心动过速， 和动脉血压下降。 压力反射增强 据报道，交感神经抑制和交感神经兴奋减弱 怀孕动物，尽管其机制尚未明确。 这 黄体酮的主要代谢物，3-α-羟基-二氢黄体酮 (3-α-OH-DHP) 在怀孕期间升高，是一种强效阳性物质 中枢神经系统 (CNS) 抑制性 GABA-A 受体的调节剂。 向原始动物外源施用 3-α-OH-DHP 模拟 怀孕的影响：交感神经抑制增强，交感神经兴奋 很可能是通过中枢神经系统机制减弱的。 重要的是，阻止 妊娠期内源性 3-α-OH-DHP 的形成逆转了 交感神经抑制减弱。 以往的研究主要集中在增强 动脉压力反射交感神经抑制。 在目前的提案中， 实验旨在评估衰减机制 交感神经兴奋反应（可能不是动脉压力反射介导的）。 这 一般假设是要检验的，即交感神经兴奋在 妊娠与中枢神经系统 GABA 能机制有关 参与心血管功能调节的部位。 三 将评估可能性：增加的抑制影响 除动脉压力感受器外的外周受体，抑制增加 中枢神经系统的影响，以及头侧兴奋作用的降低 延髓腹外侧区（RVLM，心血管交感神经的脑干部位） 前运动神经元）。 处女和怀孕大鼠的实验将评估 Fos 蛋白在已识别神经元群中的中枢神经系统表达 参与中央心血管控制以下操作 通常会增加或减少传出交感神经的活动。 传出 交感神经活动将在其他实验中被记录，其中 抑制性传入输入、中枢神经系统抑制性影响和兴奋性输入 RVLM 将被更改。 了解抑制机制 正常怀孕动物的交感兴奋反应具有重要意义 对高血压疾病或妊娠的影响 具有夸张的交感神经兴奋反应。