Vasomotor Sympathetic Activity during Early Pregnancy in Humans

人类妊娠早期的血管舒缩交感神经活动

• 批准号: 7587949
• 负责人: QI FU
• 金额: $ 23.84万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7587949
• 关键词: Address; Adrenergic Agents; Affect; Age; Asians; Blood Pressure; Blood Volume; Cardiac Output; Cardiovascular Diseases; Cardiovascular system; Caucasians; Caucasoid Race; Cause of Death; Cessation of life; Characteristics; Congestive Heart Failure; Coronary; Data; Development; Exploratory/Developmental Grant; Exposure to; Failure; Fetal Death; Fright; Functional disorder; Funding; Future; Goals; Grant; Human; Hyperactive behavior; Hypertension; Hypertension induced by pregnancy; Hypoxia; Knowledge; Life; Light; Low Prevalence; Maintenance; Morbidity - disease rate; Mothers; Myocardial Ischemia; Nature; Nerve; Orthostasis; Outcome; Patients; Peripheral; Play; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Histories; Pregnant Women; Publishing; Race; Recording of previous events; Regulation; Research; Research Project Grants; Risk; Role; Staging; Sympathetic Nervous System; Syndrome; Techniques; Testing; United States; Vascular resistance; Vasomotor; Woman; adrenergic; follow-up; hemodynamics; indexing; innovation; insight; neuromechanism; neuroregulation; normotensive; novel; pressure; public health relevance; theories

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.

描述（由申请人提供）：妊娠高血压影响美国高达10%的孕妇，最严重的形式，先兆子痫，是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。交感神经肾上腺素能控制在人类血压维持中起重要作用。交感神经活动在正常妊娠中增加，在妊娠晚期的妊娠高血压或先兆子痫妇女中甚至更大。然而，目前还完全不清楚交感神经功能亢进是否在正常妊娠早期发展，在整个妊娠期间保持高水平，或者这种交感神经激活是否只发生在足月，为妊娠高血压或先兆子痫提供底物。我们发现，在5个健康的白人妇女，在怀孕早期，交感神经活动是非常高的（类似于充血性心力衰竭患者），而矛盾的是，他们的血压和外周血管阻力是正常的。这一发现与关于神经激素对正常妊娠的适应的流行观点相反，这表明交感神经激活仅发生在妊娠晚期，据我们所知，没有发表的人类妊娠早期的神经记录。令人惊讶的是，一名怀孕早期的亚洲妇女的交感神经活动增加不那么明显，这增加了显著的交感神经激活可能是种族依赖的可能性。这些观察结果需要在更多的孕妇中进行验证。因此，本研究项目的目的是确定是否显着的交感神经激活是一个普遍的特点，早期妊娠（d 8周妊娠）在人类和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测试的假设，即血管交感神经活动显着增加，在怀孕早期，尽管正常的血压在健康的高加索人，但不是亚洲妇女。这一目标将通过利用显微神经摄影术的创新技术来实现。如果获得的结果与我们的试点数据相同，它将从根本上改变对妊娠期血压如何调节的理解，并为妊娠高血压及其最可怕的结局-先兆子痫的发展提供见解。公共卫生关系：怀孕期间发生的高血压是母亲和婴儿死亡或发病的一个主要原因，已经发现交感神经活动的增加与这个问题有关。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跃是否在怀孕早期发展，在整个怀孕期间保持高水平，或者这种交感神经激活是否只发生在人类中。本项目的主要目标是解决这些问题。所获得的结果将提供新的见解，血压是如何调节交感神经系统在正常怀孕期间，特别是在人类怀孕早期。