Mechanisms of Pregnancy Induced Hypertension

妊娠高血压的机制

• 批准号: 7105118
• 负责人: Babbette LaMarca
• 金额: $ 5.19万
• 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/7105118
• 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）：本研究的目的是确定介导妊娠高血压的机制。本研究的中心假设是子宫胎盘灌注压降低通过减少肾压尿钠排泄引起高血压。由于胎盘和/或白细胞来源的细胞因子引起内皮细胞活化，导致内皮素形成增强，从而发生压力性尿钠排泄减少。这些异常减少肾血浆流量和肾小球滤过，从而降低肾钠排泄功能。为了检验这一假设，将在通过长期降低子宫灌注压（RUPP）产生的慢性妊高征的清醒、慢性仪器化大鼠模型中检查动脉压、肾脏、激素和内皮功能。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、性类固醇和内皮素产生之间的相互作用。要解决的具体目的是：1）检验子宫胎盘灌注压慢性降低期间心血管和肾功能异常是由于炎症细胞因子（如TNF α和IL-6）的母体血浆水平升高所致的假设; 2）检验雌激素和/或孕酮增强内皮活化和对TNF α和IL-6的高血压反应的假设。