EFFECT OF PVN ANDROGEN RECEPTOR KNOCKDOWN ON HYPERTENSION DEVELOPMENT

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。雄激素会加剧高血压的发展。这种预防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：下丘脑室旁核是一个关键的前脑部位，通过增加交感神经向心血管系统的流出参与高血压过程。PVN受累的高峰似乎是在高血压的发育阶段，这与交感神经活动的高峰和雄激素分泌的激增相对应。因此，本实验旨在验证以下假设，即下丘脑室旁核雄激素作用的损害将减轻遗传性高血压的发展。该项目将利用RNA沉默的方法，在高血压前期选择性地损害男性SHR PVN中的雄激素受体功能，然后通过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.