CONTROL OF BLOOD PRESSURE AND BODY FLUIDS IN PREGNANCY

妊娠期血压和体液的控制

• 批准号: 3325805
• 负责人: LORI L WOODS
• 金额: $ 10.04万
• 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 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3325805
• 关键词: blood coagulation disorders; blood pressure; blood volume; body water; cardiovascular pharmacology; disease /disorder model; dogs; extracellular; glomerular filtration; homeostasis; ischemia; kidney circulation; norepinephrine; pregnancy circulation disorder; pregnancy toxemia /hypertension; prostaglandins; proteinuria; radioassay; renal tubular transport; renin angiotensin system; reproductive system circulation; salt intake; saluresis; uterus; vasoconstrictors; vasopressins

The hypertensive disorders of pregnancy are a major contributor to perinatal morbidity and mortality and as such they represent an important public health problem. The main objectives of the proposed studies are to develop a model of uteroplacental ischemia-induced hypertension in the pregnant dog and then to study the specific renal and hormonal mechanisms involved in the development and maintenance of hypertension in this model. The specific aims of these studies are 1) to develop a model of controllable, reversible uteroplacental ischemia-induced hypertension in the chronically instrumented pregnant dog by precisely servo-controlling uterine perfusion pressure at a reduced level for one to two weeks while continuously monitoring systemic arterial pressure, 2) to characterize this model of hypertension in pregnancy and evaluate it as a suitable model of pregnancy- induced hypertension (PIH) in women by looking at the variables that are often abnormal in PIH. Specifically, we plan to determine whether proteinuria, reduced blood volume, increased extracellular fluid volume, reduced renal plasma flow (RPF) and glomerular filtration rate (GFR), glomerular lesions, and coagulation defects are present in our model, 3) to test the hypothesis that a vasoconstrictor substance is released into the maternal circulation by the uterus/placenta during reductions in uterine perfusion pressure, and if so, to attempt to identify this substance and to determine the time course of its release, 4) to determine the renal mechanisms involved in the development and maintenance of hypertension, including changes in RPF, GFR, and tubular sodium handling, 5) to test the hypothesis that the renin- angiotensin system is involved in the development and maintenance of hypertension by fixing the activity of this system before reducing uterine perfusion pressure, 6) to test the hypothesis that the prostaglandin system is involved in the development and maintenance of hypertension by blocking prostaglandin synthesis before reducing uterine perfusion pressure, 7) to test the concept that the degree of hypertension developed is proportional to the level of sodium intake, and 8) to determine the degree to which uterine blood flow is capable of autoregulation during reductions in perfusion pressure, both acutely and chronically, and if autoregulation does occur, to test the hypotheses that the renin-angiotensin and prostaglandin systems are involved in mediating this response.

妊娠期高血压疾病是一个主要因素 围产期发病率和死亡率，因此， 重要的公共卫生问题。 的主要目标 建议的研究是建立一个子宫胎盘模型， 缺血性高血压在怀孕的狗，然后， 研究特定的肾脏和激素机制参与 在该模型中高血压的发展和维持。 这些研究的具体目标是：（1）建立一个模型， 可控的、可逆的子宫胎盘缺血诱导的 高血压的慢性仪器怀孕狗， 精确地伺服控制子宫灌注压， 水平一到两周，同时持续监测系统 动脉压，2）为了表征这种高血压模型， 怀孕并将其作为合适的怀孕模型进行评估- 通过观察变量， 这在妊高征中是异常的。 具体来说，我们计划 确定是否有蛋白尿，血容量减少， 细胞外液量，肾血浆流量（RPF）减少， 肾小球滤过率（GFR）、肾小球病变，以及 在我们的模型中存在凝血缺陷，3）为了测试 假设血管收缩物质被释放到 减少期间子宫/胎盘的母体循环 子宫灌注压，如果是这样，试图确定这一点， 物质，并确定其释放的时间过程，4）， 确定参与发展的肾脏机制， 维持高血压，包括RPF、GFR和 肾小管钠处理，5）测试假设，肾素- 血管紧张素系统参与发展， 通过固定该系统的活性来维持高血压 在降低子宫灌注压之前，6）为了测试 假设前列腺素系统参与了 阻断高血压的发生和维持 减少子宫灌注前前列腺素合成 压力，7）测试的概念，高血压的程度 发展是成比例的钠摄入量的水平，和8）， 确定子宫血流能够达到的程度 灌注压降低期间的自动调节， 急性和慢性，如果发生自动调节，以测试 假设血管紧张素和前列腺素 系统参与调解这种反应。