CONTROL OF BLOOD PRESSURE AND BODY FLUIDS IN PREGNANCY

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，因此它们代表了一种 重要的公共卫生问题。该计划的主要目标 建议的研究是开发一种子宫胎盘模型 妊娠犬脑缺血性高血压的实验研究 研究特定的肾脏和荷尔蒙机制参与 在这个模型中高血压的发展和维持。 这些研究的具体目标是1)开发一个模型 可控性、可逆性子宫胎盘缺血 慢性仪器化妊娠犬的高血压 精确的伺服控制子宫灌注压 持续一到两周的水平，同时持续监测系统 动脉压，2)用来描述这种高血压模型 并评估它是一种合适的怀孕模式- 从变量看女性诱发性高血压(PIH) 这在妊高征患者中通常是不正常的。具体地说，我们计划 确定蛋白尿，血容量减少，是否增加 细胞外液容量、肾血浆流量(RPF)减少和 肾小球滤过率(GFR)、肾小球病变和 我们的模型中存在凝结缺陷，3)为了测试 假设一种血管收缩物质被释放到 减胎期间子宫/胎盘的母体循环 子宫灌注压，如果是的话，尝试确定这一点 物质并确定其释放的时间进程，4) 确定参与发育和发育的肾脏机制 高血压的维持，包括RPF、GFR和 管状钠处理，5)以验证肾素- 血管紧张素系统参与了血管紧张素系统的发育和 通过固定这一系统的活动来维持高血压 在降低子宫灌注压之前，6)测试 假设前列腺素系统参与了 阻滞型高血压病的发生与维持 减少子宫灌注量前的前列腺素合成 压力，7)测试高血压程度的概念 发展与钠的摄入量成正比，8)到 确定子宫血流量能够达到的程度 灌流压力降低时的自动调节，两者 如果确实发生了自动调节，则测试 肾素-血管紧张素和前列腺素的假设 系统参与了这一反应的调解。

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.