STUDIES OF UTEROPLACENTAL CIRCULATION

子宫胎盘循环的研究

• 批准号: 6181332
• 负责人: CHARLES RICHARD ROSENFELD
• 金额: $ 34.32万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6181332
• 关键词: SDS polyacrylamide gel electrophoresis; angiogenesis; angiotensin II; angiotensin receptor; autoradiography; cardiovascular function; cyclic GMP; estrogens; growth factor receptors; hormone regulation /control mechanism; hypertrophy; muscle proteins; nitric oxide; placenta; potassium channel; pregnancy circulation; protein structure function; radioimmunoassay; receptor expression; sheep; umbilical cord; vascular smooth muscle; vasoconstriction; western blottings

The long term objective of this project is to determine those factors in the maternal and fetal compartments responsible for maintaining and regulating uteroplacental (UtBF) and umbilicoplacental blood flow, and how they relate to general cardiovascular adaptation during pregnancy. In the proposed funding period, efforts will be focused on 3 main areas: the vascular effects of estrogen, angiotensin II (ANG II) receptor (ATR) expression and function, and smooth muscle protein expression and function. To do this 5 Specific Aims will be addressed: 1)to determine the role of nitric oxide, cGMP and K+ channels in mediating estrogen- induced vasodilation and modulation of UtBF in pregnancy; 2) to clarify what peripherally released vasoconstrictor(s) mediates ANG II induced uterine vasoconstriction; 3) to determine how vascular smooth muscle ATR expression is regulated in pregnancy; 4) to investigate the hormonal and/or growth factors and inhibitors of cell division that account for uterine vascular growth and hypertrophy in pregnancy; and 5) to examine the role and mechanism whereby estrogen may modulate uteroplacental and umbilicoplacental blood flows prior to and during parturition. To achieve these aims we will study chronically instrumented nonpregnant ewes and pregnant ewes with their fetus. In vivo studies are designed to answer specific questions about physiologic responses to and mechanisms of action by estrogen, ANG II or alpha-agonists in maternal uterine circulation, and the effects of parturition on both maternal and fetal placental vasculature. In vitro studies using tissues from these animals with patch-clamp techniques, contractile protein measurements, western or northern analysis, cell cultures, and measurement of vascular stresses will permit us to more accurately determine the cellular and molecular mechanisms responsible for adaptive changes to pregnancy. The results of the proposed studies will provide important insights into biochemical cellular and physiologic adaptive mechanisms that are necessary for the successful outcome of pregnancy and the maintenance of fetal well-being, which in turn will improve our understanding of problems associated with abnormal pregnancy and development, thereby permitting us to address them in a more meaningful way.

该项目的长期目标是确定这些因素 在母体和胎儿室中负责维持和 调节子宫胎盘 (UtBF) 和脐胎盘血流，以及 它们与怀孕期间的一般心血管适应有何关系。 在拟议的资助期内，工作重点将集中在三个主要领域： 雌激素、血管紧张素 II (ANG II) 受体 (ATR) 的血管作用 表达和功能，以及平滑肌蛋白的表达和 功能。 为此，将解决 5 个具体目标：1) 确定 一氧化氮、cGMP 和 K+ 通道在介导雌激素中的作用 妊娠期间诱导血管舒张和 UtBF 调节； 2）澄清 外周释放的血管收缩剂介导 ANG II 诱导的什么 子宫血管收缩; 3）如何确定血管平滑肌ATR 妊娠期间表达受到调节； 4）检查荷尔蒙 和/或生长因子和细胞分裂抑制剂 妊娠期子宫血管生长和肥大； 5) 检查 雌激素调节子宫胎盘的作用和机制 分娩前和分娩期间脐胎盘血流。 到 为了实现这些目标，我们将研究长期使用仪器的非怀孕者 母羊和怀孕的母羊及其胎儿。 设计体内研究 回答有关生理反应的具体问题 雌激素、ANG II 或 α 激动剂对母体的作用机制 子宫循环，以及分娩对产妇和产妇的影响 胎儿胎盘脉管系统。 使用这些组织进行体外研究 使用膜片钳技术、收缩蛋白测量的动物， 西方或北方分析、细胞培养和血管测量 压力将使我们能够更准确地确定细胞和 负责妊娠适应性变化的分子机制。 这 拟议研究的结果将为以下问题提供重要见解： 生化细胞和生理适应机制 成功妊娠和维持妊娠所必需的 胎儿的健康，这反过来又会提高我们对 与异常妊娠和发育相关的问题，从而 使我们能够以更有意义的方式解决这些问题。