Vasomotor Sympathetic Activity during Early Pregnancy in Humans

描述(申请人提供)：在美国，妊娠高血压综合征影响高达10%的孕妇，其中最严重的形式先兆子痫是导致孕产妇和胎儿死亡或发病的主要原因。虽然这些并发症的机制尚不清楚，但已提出妊娠高血压综合征或先兆子痫与肾上腺素能亢进状态有关，这可能有助于这些疾病的病理生理学。交感肾上腺素能控制在维持人类血压方面起着重要作用。研究发现，交感神经活性在正常妊娠时增加，在妊娠高血压综合征或妊娠晚期先兆子痫的妇女中甚至更强。然而，交感神经过度活动是在正常妊娠早期发展起来的，并在整个妊娠过程中保持高水平，还是这种交感神经激活只发生在足月，为妊娠高血压综合征或先兆子痫提供底物，目前还完全不清楚。我们在5名健康的高加索妇女中发现，在妊娠早期，交感神经活动极高(与充血性心力衰竭患者相似)，而她们的血压和外周血管阻力却正常。这一发现与关于神经激素对正常妊娠的适应的普遍看法相反，后者认为交感神经激活只发生在妊娠晚期，据我们所知，没有发表过人类怀孕早期的神经记录。令人惊讶的是，一名怀孕早期的亚洲女性的交感神经活动增加得不那么明显，这增加了显著的交感神经激活可能与种族有关的可能性。这些观察结果需要在更多的孕妇身上得到证实。因此，本研究项目的目的是确定显著的交感神经激活是否是人类早期妊娠(孕8周)的普遍特征，以及交感神经控制在正常妊娠中的作用。为此，该项目的具体目标将检验这一假设，即尽管健康的高加索女性的血压正常，但亚洲女性的血管运动交感神经活性在怀孕早期显著增加。这一目标将通过利用创新的显微神经学技术来实现。如果获得的结果与我们的试点数据相同，这将从根本上改变人们对怀孕期间血压调节方式的理解，并为妊娠期高血压的发展及其最令人担忧的结局--先兆子痫提供见解。公共卫生相关性：妊娠期高血压是导致母亲和婴儿死亡或发病的主要原因之一，已发现交感神经活动的增加与这一问题有关。交感神经活动在保持血压稳定方面起着重要作用。然而，在怀孕最后几个月血压正常的孕妇中，也发现交感神经活动增加。目前还完全不清楚交感神经过度活动是在怀孕早期发展起来的，在整个怀孕过程中保持高水平，还是这种交感神经激活只在人类足月时发生。该项目的主要目标是解决这些问题。所获得的结果将为交感神经系统如何在正常怀孕期间调节血压提供新的见解，特别是在人类怀孕早期。

DESCRIPTION (provided by applicant): Pregnancy-induced hypertension affects up to 10% of pregnant women in the United States, and the most severe form, preeclampsia, is the leading cause of maternal and fetal death or morbidity. Although the mechanisms for such complications are unclear, it has been proposed that either pregnancy-induced hypertension or preeclampsia is associated with a hyperadrenergic state, which may contribute to the pathophysiology of these conditions. Sympathetic adrenergic control plays an important role in blood pressure maintenance in humans. Sympathetic activity was found to increase in normal pregnancy and to be even greater in women with pregnancy-induced hypertension or preeclampsia in late pregnancy. However, it is completely unknown whether sympathetic hyperactivity develops early in normal pregnancy, remaining high throughout the entire gestation, or whether this sympathetic activation only occurs at term, providing the substrate for pregnancy-induced hypertension or preeclampsia. We found in 5 healthy Caucasian women that during early pregnancy, sympathetic activity was extremely high (similar to those of congestive heart failure patients), while paradoxically their blood pressure and peripheral vascular resistance were normal. This finding is counter to the prevailing wisdom regarding the neurohormonal adaptation to normal pregnancy, which suggests that sympathetic activation occurs only in late pregnancy, and to our knowledge, there are no published nerve recordings in early human pregnancy. Surprisingly, one Asian woman in early pregnancy had a much less prominent increase in sympathetic activity, raising the possibility that marked sympathetic activation may be race-dependent. These observations need to be verified in more pregnant women. Thus, the purpose of this research project is to determine whether marked sympathetic activation is a universal characteristic of early pregnancy (d 8 weeks of gestation) in humans and the role of sympathetic neural control in normal pregnancy. To this end, the specific aim of this project will test the hypothesis that vasomotor sympathetic activity increases dramatically during early pregnancy despite a normal blood pressure in healthy Caucasian but not Asian women. This objective will be accomplished by utilizing the innovative technique of microneurography. If the results obtained are the same as in our pilot data, it would radically alter the understanding of how blood pressure is regulated in pregnancy as well as provide insights into the development of gestational hypertension and its most feared outcome, preeclampsia. PUBLIC HEALTH RELEVANCE: High blood pressure occurring during pregnancy is one major cause of death or morbidity for both mothers and babies, and it has been found that an increase in sympathetic activity is related to this problem. Sympathetic activity plays an important role in keeping blood pressure stable. However, increased sympathetic activity was also found in pregnant women whose blood pressure was normal during the latter months of their pregnancies. It is completely unknown whether sympathetic hyperactivity develops early during pregnancy, remaining high throughout the entire gestation, or whether this sympathetic activation only occurs at term in humans. The primary goal of this project is to address these issues. Results obtained will provide novel insights into how blood pressure is regulated by the sympathetic nervous system during normal pregnancy, particularly during early pregnancy in humans.