权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Studies of Uteroplacental Circulation

子宫胎盘循环的研究

基本信息

批准号：
7384514
负责人：
CHARLES RICHARD ROSENFELD
金额：
$ 35.45万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-09-01 至 2009-07-20
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7384514
关键词：
AGTR2 gene Address Agonist Angiotensin II Animals Arachidonic Acids Arteries Attenuated Biochemical Birth Blood Circulation Blood Vessels Blood flow Calcium Cardiovascular system Cell Communication Cells Constriction procedure Cytochrome P450 Development Enzymes Estradiol Estrogen Receptors Estrogens Fetal Growth Fetus Figs - dietary Funding In Vitro Maintenance Mediating Modeling Modification Molecular Mothers Nitric Oxide Nitric Oxide Synthase Type I Nutrient Outcome Pathogenesis Patient currently pregnant Perfusion Peripheral Personal Satisfaction Physiological Physiology Placenta Plasma Play Potassium Channel Pregnancy Pregnancy Outcome Progress Reports Protein Isoforms Refractory Regulation Relaxation Reporting Research Design Role Sheep Signal Pathway Type 2 Angiotensin II Receptor Uteroplacental Circulation Uterus Vascular Smooth Muscle Vasoconstrictor Agents Woman fetal improved in vivo insight instrument instrumentation lipid mediator novel strategies pregnancy disorder pressure prevent response

项目摘要

DESCRIPTION (provided by applicant): The long term objective of this project has been to characterize and understand those factors and mechanisms in the mother and fetus that contribute to the regulation and increases in uteroplacental (UtBF) and umbilicoplacental (UmBF) during pregnancy, respectively, and how they relate to the general cardiovascular adaptation in pregnancy and development. In the proposed project, efforts will focus on studying the mechanisms that regulate the vascular responses to estrogen, basal UtBF in pregnancy, and attenuated uteroplacental responses to vasoconstrictors. To do this 4 specific aims will be addressed: 1) to further characterize the expression and function of uterine vascular smooth muscle (VSM) nNOS in responses to estrogen and pregnancy; 2) to delineate the role of VSM BK[Ca] and other K+-channels in the maintenance and modulation of UtBF in pregnancy; 3) to characterize and delineate the mechanisms that regulate UtBF during parturition; and 4) to determine the role lipid mediators derived from arachidonic acid via the cytochrome P450 (CYP) enzymes play in estrogen responses and the modulation of UtBF in pregnancy. To achieve these aims, we will study chronically instrumented nonpregnant and pregnant ewes with their fetus. In in vivo studies, we will "isolate" the uterus by instrumentation and study uterine vascular responses to multiple agonists and antagonists independent of systemic effects. This permits us to answer specific questions about uterine responses to exogenous E2beta, the role of nitric oxide isoforms, activation of K+-channels, involvement of P450 enzymes, and if endogenous placental estrogen regulates each of these during parturition. In vitro studies are designed to compliment studies in intact animals, permit exploration of signaling pathways, and to characterize estrogen receptor and channel activation and expression in pregnancy. The result of the proposed studies will provide important new understanding of mechanisms regulating blood flow, which are essential to the successful outcome of pregnancy, normal fetal growth, and the maintenance of fetal well-being. This will contribute to our understanding of abnormal fetal growth and how to prevent adverse fetal outcomes.

描述(由申请人提供)：这个项目的长期目标是描述和了解母亲和胎儿在怀孕期间分别调节和增加子宫胎盘(UtBF)和脐胎盘(UMBF)的因素和机制，以及它们与怀孕和发育期间一般心血管适应的关系。在拟议的项目中，将致力于研究调节血管对雌激素的反应、妊娠期基础UtBF以及减弱子宫胎盘对血管收缩的反应的机制。为此，将针对4个具体目标：1)进一步表征子宫血管平滑肌(VSM)nNOS在雌激素和妊娠反应中的表达和功能；2)描述VSM BK[Ca]和其他K+通道在妊娠UtBF维持和调节中的作用；3)表征和描述分娩期间调节UtBF的机制；以及4)确定花生四烯酸通过细胞色素P450(CYP)酶衍生的脂质介质在雌激素反应和妊娠UtBF调节中的作用。为了实现这些目标，我们将研究长期使用仪器的未怀孕和怀孕的母羊及其胎儿。在活体研究中，我们将通过仪器“隔离”子宫，并研究子宫血管对多种激动剂和拮抗剂的反应，而不受全身影响的影响。这使我们能够回答有关子宫对外源性E2beta的反应、一氧化氮亚型的作用、K+通道的激活、P450酶的参与以及内源性胎盘雌激素是否在分娩期间调节这些因素的具体问题。体外研究的目的是补充在完整动物身上的研究，允许探索信号通路，并表征怀孕期间雌激素受体和通道的激活和表达。这些研究的结果将对血流调节机制提供重要的新的理解，而血流调节机制对于妊娠的成功结局、胎儿的正常发育和维持胎儿的健康至关重要。这将有助于我们了解胎儿发育异常以及如何预防不良胎儿结局。