EFFECT OF PVN ANDROGEN RECEPTOR KNOCKDOWN ON HYPERTENSION DEVELOPMENT

PVN 雄激素受体敲低对高血压发展的影响

• 批准号: 7381111
• 负责人: DOUGLAS S MARTIN
• 金额: $ 1.68万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381111
• 关键词: EFFECT; PVN; ANDROGEN; RECEPTOR; KNOCKDOWN

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Androgens amplify hypertension development. The mechanisms of this prohypertensive effect remain to be determined. Current evidence supports the view that the hypothalamic paraventricular nucleus is a key forebrain site involved in the hypertensive process by way of increasing sympathetic outflow to the cardiovascular system. Peak involvement of the PVN appears to be during the developmental stages of hypertension which corresponds to a time of peak sympathetic activity and a surge in androgen secretion. Accordingly, the proposed experiments are designed to test the hypothesis that impairment of androgen action in the hypothalamic paraventricular nucleus will attenuate the development of genetic hypertension. The project will make use of an RNA silencing approach to selectively impair androgen receptor function in the PVN of male SHR at the prehypertensive stage and then track blood pressure through the developmental stages (~6 weeks) of hypertension using radiotelemetry.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。雄激素会加剧高血压的发展。这种抗高血压作用的机制仍有待确定。目前的证据支持这样的观点，即下丘脑室旁核是通过增加心血管系统交感神经流出参与高血压过程的关键前脑部位。 PVN 的高峰参与似乎是在高血压的发展阶段，这对应于交感神经活动高峰和雄激素分泌激增的时期。因此，所提出的实验旨在检验以下假设：下丘脑室旁核中雄激素作用的损害将减弱遗传性高血压的发展。该项目将利用 RNA 沉默方法选择性损害高血压前期男性 SHR 的 PVN 中的雄激素受体功能，然后使用无线电遥测技术在高血压的发展阶段（约 6 周）跟踪血压。