CONTROL OF BLOOD PRESSURE AND BODY FLUIDS IN PREGNANCY

妊娠期血压和体液的控制

• 批准号: 3325807
• 负责人: LORI L WOODS
• 金额: $ 9.65万
• 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/3325807
• 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.

随着胎儿在妊娠期的成长，几乎所有的氧气和 生长所需的营养物质从母体循环中获得 穿过胎盘 胎儿的废物也被清除， 路线 因此，这并不奇怪，在这种情况下，产妇 子宫胎盘血流量减少通常与 胎儿宫内发育迟缓。 很明显，理解 控制妊娠期子宫血流的机制将是 这对预防此类情况很重要。 可惜 子宫胎盘循环的生理调节 - 不太了解 假设肾素-血管紧张素系统 参与控制妊娠期子宫胎盘血流， 然而，肾素和血管紧张素在调节子宫血液中的作用 血流和心血管动力学在怀孕仍然不清楚。 这些研究的目标是：1）确定 子宫胎盘血流自动调节在慢性仪器 怀孕的狗，并测试假设，肾素-血管紧张素和/或 前列腺素系统介导的自我调节行为，通过比较 在存在和不存在药理学作用下的自动调节曲线 这两个系统的抑制剂，2）以确定的作用， 肾素-血管紧张素系统在控制子宫胎盘血流中的作用，以及 检验血管紧张素II纯粹是一种血管收缩剂的假设， 子宫胎盘循环和巯甲丙脯酸减少子宫胎盘 通过降低动脉压以外的机制进行血流，或 阻断肾素-血管紧张素系统 这些概念将得到检验 通过在输注期间伺服控制子宫灌注压 血管紧张素II或巯甲丙脯酸，并通过比较对其他 阻断肾素-血管紧张素系统的药物，3）确定 子宫和肾脏的肾素分泌对血浆的相对贡献 妊娠中的肾素活性，并检验子宫和 和肾脏肾素分泌增加，以响应减少灌注 压力在有意识的怀孕狗，和4）测试的假设 血管紧张素II在离体子宫血管中起血管收缩剂的作用 以及来自孕妇的血管平滑肌（子宫和股动脉） 狗本质上对血管紧张素II和去甲肾上腺素不太敏感 比未怀孕的动物的要多。