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Estrogen receptor-beta in the paraventricular nucleus and rostroventrolateral medulla plays an essential protective role in aldosterone/salt-induced hypertension in female rats.

Authors: Xue, B  Zhang, Z  Beltz, TG  Johnson, RF  Guo, F  Hay, M  Johnson, AK 
Citation: Xue B, etal., Hypertension. 2013 Jun;61(6):1255-62. doi: 10.1161/HYPERTENSIONAHA.111.00903. Epub 2013 Apr 22.
Pubmed: (View Article at PubMed) PMID:23608653
DOI: Full-text: DOI:10.1161/HYPERTENSIONAHA.111.00903

The identification of the specific estrogen receptor (ER) subtypes that are involved in estrogen protection from hypertension and their specific locations in the central nervous system is critical to our understanding and design of effective estrogen replacement therapies in women. Using selective ER agonists and recombinant adeno-associated virus (AAV) carrying small interference (si) RNA to silence either ERalpha (AAV-siRNA-ERalpha) or ERbeta (AAV-siRNA-ERbeta), the present study investigated regional specificity of different ER subtypes in the protective actions of estrogen in aldosterone (Aldo)-induced hypertension. Intracerebroventricular infusions of either diarylpropionitrile, a selective ERbeta agonist, or propyl-pyrazole-triol, a selective ERalpha agonist, attenuated Aldo/NaCl-induced hypertension in ovariectomized rats. In contrast, intracerebroventricular injections of siRNA-ERalpha or siRNA-ERbeta augmented Aldo-induced hypertension in intact females. Site-specific paraventricular nucleus (PVN) or rostroventrolateral medulla (RVLM) injections of siRNA-ERbeta augmented Aldo-induced hypertension. However, rats with PVN or RVLM injections of siRNA-ERalpha did not significantly increase blood pressure induced by Aldo. Real-time polymerase chain reaction analyses of the PVN and RVLM of siRNA-injected rat confirmed a marked reduction in the expression of ERalpha and ERbeta. In cultured PVN neurons, silencing either ERalpha or ERbeta by culturing PVN neurons with siRNA-ERalpha or siRNA-ERbeta enhanced Aldo-induced reactive oxygen species production. Ganglionic blockade after Aldo infusion showed an increase in sympathetic activity in ERbeta knockdown rats. These results indicate that both PVN and RVLM ERbeta, but not ERalpha in these nuclei, contribute to the protective effects of estrogen against Aldo-induced hypertension. The brain regions responsible for the protective effects of estrogen interaction with ERalpha in Aldo-induced hypertension still need to be determined.


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RGD Object Information
RGD ID: 7364951
Created: 2013-10-14
Species: All species
Last Modified: 2013-10-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.