Either PVN or RVLM injections of adeno‐associated virus‐siRNA to silence estrogen receptor β (ERβ) produces augmentation of aldosterone/NaCl‐induced hypertension in female rats

Abstract

Previous studies have shown that icv injections of recombinant adeno‐associated virus (AAV) carrying small interference (si) RNA to silence either ERα (AAV‐siRNA‐ERα) or ERβ (AAV‐siRNA‐ERβ) augments aldosterone (ALDO)‐induced hypertension (HT) in female rats. The present study investigated regional specificity of different ER subtypes in the protective actions of estrogen in the brain. Blood pressure was measured in female rats with the use of telemetry implants. ALDO (750 ng/h) was administered s.c. via osmotic pump and 1% NaCl was provided for drinking. At the same time, PVN or RVLM injections of AAV‐siRNA‐ERα, AAV‐siRNA‐ERβ or scrambled siRNA (AAV‐siRNA‐SCM) were used to knock down ERα and ERβ subtypes. Either PVN or RVLM injections of AAV‐siRNA‐ERβ augmented ALDO‐induced HT (Δ14.9±0.8 mmHg, n=4 and Δ15.4±2.7 mmHg, n=4, respectively). However, rats with PVN or RVLM injections of AAV‐siRNA‐ERα did not significantly increase blood pressure induced by ALDO (Δ9.8±0.7 mmHg, n=4 and Δ8.1±2.9, n=4, respectively) in comparison to AAV‐siRNA‐SCM rats (Δ6.2±1.8 mmHg, n=3 and Δ7.7±0.4 mmHg, n=3, respectively). These data indicate that both PVN and RVLM ERβ, but not ERα in these nuclei, contribute to the protective effects of estrogen against ALDO‐induced HT. The brain regions responsible for the protective effects of estrogen interaction with ERα in the development of ALDO‐induced HT still need to be determined.