ENDOTHELIN AND INTRAUTERINE GROWTH RESTRICTION

内皮素和宫内生长受限

• 批准号: 6151157
• 负责人: LARRY G THAETE
• 金额: $ 10.64万
• 依托单位: EVANSTON HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6151157
• 关键词: blood flow measurement; endothelin; hormone receptor; hormone regulation /control mechanism; immunocytochemistry; laboratory rat; messenger RNA; necrosis; nitric oxide; nitric oxide synthase; northern blottings; nucleic acid hybridization; pathologic process; placenta disorders; preeclampsia; pregnancy circulation; pregnancy disorder; pregnancy toxemia /hypertension; prenatal growth disorder; proteinuria; radioactive microsphere technique; radioimmunoassay; scintillation spectrometry; statistics /biometry; western blottings

DESCRIPTION (Adapted from the applicant's abstract): The hypothesis is that ET-1 is a critically important regulator of placental perfusion, and thus fetal growth and pregnancy outcome. The investigator will evaluate the molecular mechanisms regulating the activities of both ET-1 and NO in uteroplacental perfusion and IUGR. The investigator will also evaluate the role of endogenous ET-1 in the pathophysiology of IUGR using an ET-1 receptor antagonist. Aim 1 is to evaluate the role of ET-1 in the pathophysiology of IUGR. Aim 2 is to investigate the molecular mechanisms regulating ET-1 and NO in the pathophysiology of IUGR. In Aim 1, the investigator will evaluate the effects of an ETA on fetal and placental weight (Exp 1), uteroplacental blood flow measured with radioactive microspheres (Exp 2), maternal hypertension and proteinuria (Exp 3), and placental necrosis (Exp 4) of rats treated with a NOS inhibitor. In Aim 2, the expression of ET-1 peptide, ET-1 mRNA, ETA and ETB receptor mRNA and binding sites, endothelin converting enzyme, and NOS activity and protein mass will be measured in rats exposed to hypoxia and to NOS inhibition. Cellular localization of ET, ET receptors, and NOS isoforms will be performed with immunocytochemistry.

描述（改编自申请人的摘要）：假设是 ET-1 是胎盘灌注的极其重要的调节因子，因此 胎儿生长和妊娠结局。 调查员将评估 调节 ET-1 和 NO 活性的分子机制 子宫胎盘灌注和 IUGR。 研究人员还将评估 使用 ET-1 观察内源性 ET-1 在 IUGR 病理生理学中的作用 受体拮抗剂。 目标 1 是评估 ET-1 在 IUGR 的病理生理学。 目标2是研究分子机制 调节 ET-1 和 NO 在 IUGR 病理生理学中的作用。 在目标 1 中， 研究者将评估 ETA 对胎儿和胎盘的影响 体重（实验 1）、放射性测量的子宫胎盘血流量 微球（实验 2）、孕产妇高血压和蛋白尿（实验 3），以及 用 NOS 抑制剂治疗的大鼠胎盘坏死（实验 4）。 在目标 2 中， ET-1肽、ET-1 mRNA、ETA和ETB受体mRNA的表达和 结合位点、内皮素转化酶、NOS 活性和蛋白质 将测量暴露于缺氧和 NOS 抑制的大鼠的质量。 ET、ET 受体和 NOS 亚型的细胞定位将 通过免疫细胞化学进行。