OVARIAN HORMONE METABOLITES & NEURAL CIRCULATORY CONTROL

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， 以及动脉血压的下降。增强压力感受性反射 据报道，交感神经抑制和减弱的交感神经兴奋 怀孕的动物，尽管机制还没有很好地确定。这个 孕酮的初级代谢物3-α-羟基-二氢孕酮 (3-α-OH-DHP)在怀孕期间升高，是一种强有力的阳性反应 中枢神经系统(CNS)调节剂抑制GABA-A受体。 外源性给予处女动物3-α-OH-DHP可模拟 妊娠的影响：交感神经抑制增强和交感神经兴奋 是衰减的，很可能是通过中枢神经系统机制。重要的是，阻止 孕期内源性3-α-OH-DHP的形成逆转 减弱交感神经抑制。以前的研究主要集中在增强的 动脉压力感受性反射交感神经抑制。在目前的提案中， 实验的目的是评估衰减的机制 交感兴奋反应(可能不是由动脉压力感受性反射介导的)。这个 一般的假设将被检验，减弱交感神经兴奋在 妊娠与中枢神经系统中的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：来自以下方面的抑制影响增加 除动脉压力感受器外的外周受体，抑制作用增强 受中枢神经的影响，并减弱了嘴部的兴奋效应 延髓腹外侧部(RVLM，心血管交感神经的脑干部位 运动前神经元)。在处女和怀孕大鼠身上的实验将评估 Fos蛋白在已鉴定神经元中的中枢神经系统表达 参与中枢心血管控制后的手法 通常增加或减少传出交感神经活动。传出 交感神经活动将记录在其他实验中，在这些实验中 抑制性传入、中枢抑制性影响和兴奋性传入 到RVLM的地址将被更改。理解受抑制的机制 正常妊娠动物的交感兴奋反应将具有重要的 与高血压疾病或妊娠相关的影响 伴随着夸大的交感兴奋反应。

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.