EFFECT OF PVN ANDROGEN RECEPTOR KNOCKDOWN ON HYPERTENSION DEVELOPMENT

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。雄激素会放大高血压的发展。这种降压作用的机制尚不清楚。目前的证据支持这样的观点，即下丘脑室旁核是参与高血压过程的关键前脑部位，通过增加交感神经流出到心血管系统。PVN的受累高峰似乎出现在高血压的发育期，这与交感神经活动和雄激素分泌激增的高峰期相对应。因此，拟议的实验旨在检验下丘脑室旁核雄激素作用受损将减缓遗传性高血压发展的假设。该项目将利用RNA沉默方法，在高血压前期选择性地损害男性SHR室旁核中雄激素受体的功能，然后使用无线电遥测技术跟踪高血压发育阶段(~6周)的血压。

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.