title: Estrogen receptor-β in the paraventricular nucleus and rostroventrolateral medulla plays an essential protective role in aldosterone/salt-induced hypertension in female rats.
abstract: 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 ERα (AAV-siRNA-ERα) or ERβ (AAV-siRNA-ERβ), 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 ERβ agonist, or propyl-pyrazole-triol, a selective ERα agonist, attenuated Aldo/NaCl-induced hypertension in ovariectomized rats. In contrast, intracerebroventricular injections of siRNA-ERα or siRNA-ERβ augmented Aldo-induced hypertension in intact females. Site-specific paraventricular nucleus (PVN) or rostroventrolateral medulla (RVLM) injections of siRNA-ERβ augmented Aldo-induced hypertension. However, rats with PVN or RVLM injections of siRNA-ERα 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 ERα and ERβ. In cultured PVN neurons, silencing either ERα or ERβ by culturing PVN neurons with siRNA-ERα or siRNA-ERβ enhanced Aldo-induced reactive oxygen species production. Ganglionic blockade after Aldo infusion showed an increase in sympathetic activity in ERβ knockdown rats. These results indicate that both PVN and RVLM ERβ, but not ERα 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 ERα in Aldo-induced hypertension still need to be determined.
authors.affiliation: Department of Psychology, The University of Iowa, 11 Seashore Hall E, Iowa City, IA 52242, USA. Baojian-xue@uiowa.edu
authors.forename: Baojian
authors.initials: B
authors.lastname: Xue
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Terry G
authors.initials: TG
authors.lastname: Beltz
authors.forename: Ralph F
authors.initials: RF
authors.lastname: Johnson
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.forename: Meredith
authors.initials: M
authors.lastname: Hay
authors.forename: Alan Kim
authors.initials: AK
authors.lastname: Johnson
mesh_terms: D000450:Aldosterone / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012965:Sodium Chloride / Q000633:toxicity
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D012965:Sodium Chloride; D000450:Aldosterone
keywords: aldosterone; blood pressure; central nervous system; estrogen receptors