CONTROL OF BLOOD PRESSURE AND BODY FLUIDS IN PREGNANCY

妊娠期血压和体液的控制

• 批准号: 3325806
• 负责人: LORI L WOODS
• 金额: $ 9.47万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-04 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3325806
• 关键词: angiotensin II; captopril; disease /disorder model; dogs; kidney circulation; norepinephrine; pregnancy circulation; pregnancy toxemia /hypertension; prenatal growth disorder; prostaglandins; proteinuria; radioassay; renin angiotensin system; vasoconstrictors; vasopressins

As a fetus grows over gestation, virtually all of the oxygen and nutrients needed for growth are acquired from the maternal circulation through the placenta. Fetal waste products are also removed by this route. Therefore it is not surprising that conditions in which maternal uteroplacental blood flow is reduced are often associated with intrauterine growth retardation. It is clear that an understanding of the mechanisms that control uterine blood flow in pregnancy will be important in preventing such conditions. Unfortunately, the physiological regulation of the uteroplacental circulation remains -poorly understood. The renin-angiotensin system has been postulated to be involved in controlling uteroplacental blood flow in pregnancy, however the role of renin and angiotensin in regulating uterine blood flow and cardiovascular dynamics in pregnancy is still not clear. The goals of these studies are 1) to determine the extent to which uteroplacental blood flow autoregulates in the chronically instrumented pregnant dog and to test the hypotheses that the renin-angiotensin and/or prostaglandin systems mediate the autoregulatory behavior, by comparing autoregulation curves in the presence and absence of pharmacological inhibitors of these two systems, 2) to determine the role of the renin-angiotensin system in controlling uteroplacental blood flow, and to test the hypotheses that angiotensin II is purely a vasoconstrictor in the uteroplacental circulation and that captopril reduces uteroplacental blood flow by mechanisms other than by reducing arterial pressure or blockade of the renin-angiotensin system. These concepts will be tested by servo-controlling uterine perfusion pressure during infusion of angiotensin II or captopril, and also by comparing responses to other drugs that block the renin-angiotensin system, 3) to determine the relative contributions of uterine and renal renin secretion to plasma renin activity in pregnancy and to test the hypothesis that both uterine and renal renin secretion increase in response to reduced perfusion pressure in the conscious pregnant dog, and 4) to test the hypotheses that angiotensin II acts as a vasoconstrictor in isolated uterine vessels and that vascular smooth muscle (uterine and femoral) from the pregnant dog is intrinsically less sensitive to angiotensin II and norepinephrine than is that from nonpregnant animals.

当胎儿在怀孕期间成长时，几乎所有的氧气和 生长所需的营养是从母体循环中获得的。 通过胎盘。胎儿排泄物也是通过这种方式去除的 路线。因此，难怪母体 子宫胎盘血流量减少常与 胎儿宫内发育迟缓。很明显，对 在怀孕期间控制子宫血流的机制将是 在防止这种情况发生方面很重要。不幸的是， 子宫胎盘循环残留的生理调节 -知之甚少。肾素-血管紧张素系统被认为是 参与控制孕期子宫胎盘血流， 然而，肾素和血管紧张素在调节子宫血液中的作用 妊娠期血流与心血管动力学的关系尚不清楚。 这些研究的目标是1)确定在多大程度上 慢性内固定者子宫胎盘血流的自动调节 并测试肾素-血管紧张素和/或 前列腺素系统通过比较调节自身调节行为 药物存在和不存在时的自动调节曲线 这两个系统的抑制剂，2)确定 肾素-血管紧张素系统在控制子宫胎盘血流中的作用 测试血管紧张素II纯粹是血管收缩药的假设 子宫胎盘循环和卡托普利减少子宫胎盘 血液流动机制不是通过降低动脉压或 阻断肾素-血管紧张素系统。这些概念将得到检验 在输液过程中通过伺服控制子宫灌流压力 血管紧张素II或卡托普利，也通过比较对其他 阻断肾素-血管紧张素系统的药物，3)以确定 子宫和肾脏肾素分泌对血浆的相对贡献 肾素活性在妊娠中的变化及检验的假说 肾脏肾素分泌增加是对血流灌注减少的反应 有意识的怀孕狗的压力，以及4)检验假设 血管紧张素II在分离的子宫血管中起血管收缩作用 以及来自孕妇的血管平滑肌(子宫和股骨) 狗天生对血管紧张素II和去甲肾上腺素不敏感 而不是来自未怀孕的动物。