Genetic knockdown of estrogen receptor-alpha in the subfornical organ augments ANG II-induced hypertension in female mice

Baojian Xue, Zhongming Zhang, Terry G. Beltz, Fang Guo, Meredith Hay, Alan Kim Johnson

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The present study tested the hypotheses that 1) ERα in the brain plays a key role in the estrogen-protective effects against ANG II-induced hypertension, and 2) that the subfornical organ (SFO) is a key site where ERα mediates these protective actions. In this study, a “floxed” ERα transgenic mouse line (ERαflox) was used to create models in which ERα was knocked down in the brain or just in the SFO. Female mice with ERα ablated in the nervous system (Nestin-ERα mice) showed greater increases in blood pressure (BP) in response to ANG II. Furthermore, females with ERα knockdown specifically in the SFO [SFO adenovirus-Cre (Ad-Cre) injected ERαflox mice] also showed an enhanced pressor response to ANG II. Immunohistochemical (IHC), RT-PCR, and Western blot analyses revealed a marked reduction in the expression of ERα in nervous tissues and, in particular, in the SFO. These changes were not present in peripheral tissues in Nestin- ERα mice or Ad-Cre-injected ERαflox mice. mRNA expression of components of the renin-angiotensin system in the lamina terminalis were upregulated in Nestin-ERα mice. Moreover, ganglionic blockade on day 7 after ANG II infusions resulted in a greater reduction of BP in Nestin-ERα mice or SFO Ad-Cre-injected mice, suggesting that knockdown of ERα in the nervous system or the SFO alone augments central ANG II-induced increase in sympathetic tone. The results indicate that interfering with the action of estrogen on SFO ERα is sufficient to abolish the protective effects of estrogen against ANG II-induced hypertension.

Original languageEnglish (US)
Pages (from-to)R507-R516
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume308
Issue number6
DOIs
StatePublished - Mar 15 2015

Keywords

  • ANG II
  • Blood pressure
  • Estrogen receptor-α
  • Nervous system
  • Subfornical organ

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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