Mechanisms of Pregnancy Induced Hypertension

妊娠高血压的机制

• 批准号: 6999094
• 负责人: Babbette LaMarca
• 金额: $ 4.7万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999094
• 关键词: blood pressure; cytokine; disease /disorder model; endothelin; estrogens; female; glomerular filtration rate; inflammation; interleukin 6; kidney circulation; laboratory rat; pathologic process; postdoctoral investigator; pregnancy circulation; pregnancy toxemia /hypertension; progesterone; saluresis; tissue /cell culture; tumor necrosis factor alpha; vascular endothelium

DESCRIPTION (provided by applicant): The objective of this research is to define the mechanisms mediating pregnancy induced hypertension. The central hypothesis to be tested in this proposal is that a reduction in uteroplacental perfusion pressure causes hypertension by reducing renal-pressure natriuresis. The reduction in pressure natriuresis occurs as a result of placental and/or leukocyte-derived cytokines causing endothelial cell activation that leads to enhanced formation of endothelin. These abnormalities reduced renal plasma flow and glomerular filtration thereby decreasing renal sodium excretory function. To test this hypothesis, arterial pressure, renal, hormonal, and endothelial function will be examined in a conscious, chronically-instrumented rat model of chronic PIH produced by long-term reductions in uterine perfusion pressure (RUPP). In addition, in vitro studies utilizing endothelial cell culture will be used to determine the interaction between inflammatory cytokines, sex steroids and endothelin production. Specific aims to be addressed are: 1) To test the hypothesis that abnormalities in cardiovascular and renal function during chronic reductions in uteroplacental perfusion pressure are due to elevations in maternal plasma levels of inflammatory cytokines such as TNF alpha and IL-6; 2) To test the hypothesis that estrogens and/or progesterone enhance the endothelial activation and hypertensive response to TNF alpha and IL-6 .

描述（由申请人提供）：这项研究的目的是定义介导妊娠诱发高血压的机制。在该提案中要检验的中心假设是，子宫牙灌注压力的降低通过减少肾压纳地尿症会导致高血压。胎盘和/或白细胞衍生的细胞因子导致内皮细胞激活的胎盘和/或白细胞衍生的细胞因子会导致压力降低，从而导致内皮素的形成增强。这些异常减少了肾血浆流量和肾小球过滤，从而降低了肾脏钠排泄功能。为了检验这一假设，将在有意识的，长期蒙受的大鼠大鼠模型中检查动脉压，肾脏，激素和内皮功能，该模型是由子宫灌注压力（RUPP）长期降低产生的。此外，利用内皮细胞培养的体外研究将用于确定炎性细胞因子，性类固醇和内皮素的产生之间的相互作用。要解决的具体目的是：1）检验以下假设：子宫酸性灌注压力慢性降低过程中心血管和肾功能异常是由于母体血浆炎症细胞因子（如TNF Alpha和IL-6）的炎症细胞因子水平升高所致。 2）检验雌激素和/或孕酮增强对TNFα和IL-6的高血压反应的假设。