Mechanisms of Pregnancy Induced Hypertension

妊娠高血压的机制

• 批准号: 7270691
• 负责人: Babbette LaMarca
• 金额: $ 4.99万
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270691
• 关键词: Address; Affect; Cardiovascular system; Cessation of life; Chronic; Conscious; Cytokine Activation; Data; Disease; Elevation; Endothelial Cells; Endothelin; Estrogens; Event; Excretory function; Functional disorder; Glomerular Filtration Rate; Gonadal Steroid Hormones; Hormonal; Hypertension; Hypertension induced by pregnancy; In Vitro; Inflammatory; Interleukin-6; Kidney; Leukocytes; Mediating; Mentors; Modeling; Morbidity - disease rate; Natriuresis; Pathogenesis; Perfusion; Perinatal; Placenta; Plasma; Pre-Eclampsia; Pregnancy; Production; Progesterone; Proteinuria; Rattus; Renal Plasma Flow; Renal function; Research; Sodium; Testing; Tumor Necrosis Factor-alpha; Vascular Endothelium; cytokine; glomerular filtration; human TNF protein; in vitro Model; instrument; pressure; response; sex; tumor

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)：这项研究的目的是确定调节妊娠高血压综合征的机制。在这项建议中要检验的中心假设是，子宫胎盘灌注压的降低通过减少肾压钠尿而导致高血压。压力钠尿减少是由于胎盘和/或白细胞衍生的细胞因子引起内皮细胞激活，从而促进内皮素的形成。这些异常减少了肾脏的血浆流量和肾小球滤过，从而降低了肾脏的钠排泄功能。为了验证这一假说，我们将在长期降低子宫灌注压(RUPP)所致的慢性妊高征(PIH)的有意识的长期仪器化大鼠模型中检测动脉压、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。要解决的具体目标是：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母体血浆炎性细胞因子水平升高所致的假说；2)检验雌激素和/或孕酮增强内皮激活和高血压对肿瘤坏死因子α和IL-6的反应的假说。

项目成果

Progesterone blunts vascular endothelial cell secretion of endothelin-1 in response to placental ischemia.

• DOI: 10.1016/j.ajog.2013.03.032
• 发表时间: 2013-07
• 期刊: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
• 影响因子: 9.8
• 作者: Kiprono, Luissa V.;Wallace, Kedra;Moseley, Janae;Martin, James, Jr.;LaMarca, Babbette
• 通讯作者: LaMarca, Babbette

Progress toward identifying potential markers for preeclampsia: role of agonistic autoantibody to the angiotensin II type I receptor.

识别先兆子痫潜在标志物的进展：血管紧张素 II I 型受体激动性自身抗体的作用。

• DOI: 10.1161/hypertensionaha.109.141465
• 发表时间: 2010
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: LaMarca,Babbette