EFFECT OF PVN ANDROGEN RECEPTOR KNOCKDOWN ON HYPERTENSION DEVELOPMENT

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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.