OVARIAN HORMONE METABOLITES & NEURAL CIRCULATORY CONTROL

描述：（改编自应用程序）正常妊娠与 血容量和心输出量增加40%，轻微心动过速， 和动脉血压下降 压力感受性反射增强 交感神经抑制和减弱的交感神经兴奋已经在 怀孕的动物，虽然机制还没有得到很好的定义。 的 孕酮的初级代谢产物，3-α-羟基-二氢孕酮 （3-α-OH-DHP），这是在怀孕期间升高，是一个强有力的积极 中枢神经系统（CNS）抑制性GABA-A受体的调节剂。 向未交配动物外源性给予3-α-OH-DHP模拟了 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， 孕妇体内内源性3-α-OH-DHP的形成逆转了 减弱的交感神经抑制 以前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， 设计实验来评估衰减的机制， 交感神经兴奋反应（可能不是动脉压力反射介导的）。 的 一般假设是要测试，衰减交感兴奋期间， 妊娠与中枢神经系统GABA能机制有关 参与调节心血管功能的部位。 三 可能性将被评估：增加抑制影响，从 除动脉压力感受器以外的外周感受器，抑制性增强 中枢神经系统的影响，并减少兴奋作用的吻 延髓腹外侧（RVLM，心血管交感神经脑干部位 前运动神经元）。 在处女和妊娠大鼠中进行的实验将评估 Fos蛋白在已鉴定神经元群体中的CNS表达 参与中枢心血管控制， 正常增加或减少传出交感神经活动。 传出 交感神经活动将在其他实验中记录，其中 抑制性传入输入、CNS抑制性影响和兴奋性输入 RVLM将被更改。 了解抑制的机制 正常妊娠动物的交感神经兴奋反应将具有重要的 对高血压疾病或妊娠的影响， 交感神经兴奋反应过度

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.