%0 Journal Article
%T Nontranscriptional activation of PI3K/Akt signaling mediates hypotensive effect following activation of estrogen receptor ¦Â in the rostral ventrolateral medulla of rats
%A Wu Kay LH
%A Chen Chen-Hsiu
%A Shih Cheng-Dean
%J Journal of Biomedical Science
%D 2012
%I BioMed Central
%R 10.1186/1423-0127-19-76
%X Background Estrogen acts on the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons are located, to elicit vasodepressor effects via an estrogen receptor (ER)¦Â-dependent mechanism. We investigated in the present study nontranscriptional mechanism on cardiovascular effects following activation of ER¦Â in the RVLM, and delineated the involvement of phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway in the effects. Methods In male Sprague¨CDawley rats maintained under propofol anesthesia, changes in arterial pressure, heart rate and sympathetic neurogenic vasomotor tone were examined after microinjection bilaterally into RVLM of 17¦Â-estradiol (E2¦Â) or a selective ER¦Á or ER¦Â agonist. Involvement of ER subtypes and PI3K/Akt signaling pathway in the induced cardiovascular effects were studied using pharmacological tools of antagonists or inhibitors, gene manipulation with antisense oligonucleotide (ASON) or adenovirus-mediated gene transfection. Results Similar to E2¦Â (1 pmol), microinjection of ER¦Â agonist, diarylpropionitrile (DPN, 1, 2 or 5 pmol), into bilateral RVLM evoked dose-dependent hypotension and reduction in sympathetic neurogenic vasomotor tone. These vasodepressive effects of DPN (2 pmol) were inhibited by ER¦Â antagonist, R,R-tetrahydrochrysene (50 pmol), ASON against ER¦Â mRNA (250 pmol), PI3K inhibitor LY294002 (5 pmol), or Akt inhibitor (250 pmol), but not by ER¦Á inhibitor, methyl-piperidino-pyrazole (1 nmol), or transcription inhibitor, actinomycin D (5 or 10 nmol). Gene transfer by microinjection into bilateral RVLM of adenovirus encoding phosphatase and tensin homologues deleted on chromosome 10 (5 ¡Á 108 pfu) reversed the vasodepressive effects of DPN. Conclusions Our results indicate that vasodepressive effects following activation of ER¦Â in RVLM are mediated by nongenomic activation of PI3K/Akt signaling pathway. This study provides new insight in the intracellular signaling cascades involved in central vasodepressive functions of estrogen.
%K 17¦Â-estradiol
%K Estrogen receptor
%K Rostral ventrolateral medulla
%K Systemic arterial pressure
%K PI3K/Akt signaling pathway
%U http://www.jbiomedsci.com/content/19/1/76