Document Detail

Stimulation of sigma-1 receptor signaling by dehydroepiandrosterone ameliorates pressure overload-induced hypertrophy and dysfunctions in ovariectomized rats.
MedLine Citation:
PMID:  19769544     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Decreased dehydroepiandrosterone (DHEA) levels are associated with endothelial dysfunction and increased cardiovascular mortality in postmenopausal women. We investigated the role of DHEA, also known as sigma-1 receptor (Sig-1R) agonist, in myocardial hypertrophy, cardiac functional recovery and defined mechanisms of cardioprotective action. METHODS: Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis. DHEA (15 and 30 mg/kg) was administered orally once a day for 14 days starting from 2 weeks after aortic banding. RESULTS: Time course study indicated that left ventricle (LV) weight:body weight (BW) ratio increased time-dependently from 1 to 4 weeks after pressure-overload (PO) with significant inversed regulation of Sig-1R expression. Treatment with the Sig-1R agonist, DHEA, significantly attenuated PO-induced myocardial hypertrophy with increased expression of Sig-1R in the LV. DHEA also attenuated hypertrophy-induced impaired LV end diastolic pressure, LV developed pressure and LV contractility (+/- dp/dt(max)). DHEA treatment significantly restored PO-induced impaired eNOS and Akt activity in the LV. CONCLUSION: We report, for the first time to our knowledge, the potential role of Sig-1R expression in the heart to attenuate PO-induced hypertrophy in ovariectomized rats. DHEA treatment protects against PO-induced cardiac injury via upregulation of Sig-1R and stimulation of Sig-1R-mediated Akt-eNOS signaling.
Md Shenuarin Bhuiyan; Kohji Fukunaga
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Expert opinion on therapeutic targets     Volume:  13     ISSN:  1744-7631     ISO Abbreviation:  Expert Opin. Ther. Targets     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-22     Completed Date:  2009-12-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101127833     Medline TA:  Expert Opin Ther Targets     Country:  England    
Other Details:
Languages:  eng     Pagination:  1253-65     Citation Subset:  IM    
Tohoku University, Graduate School of Pharmaceutical Sciences, Department of Pharmacology, Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Japan.
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MeSH Terms
Blood Pressure / drug effects
Cardiotonic Agents / administration & dosage,  pharmacology*
Dehydroepiandrosterone / administration & dosage,  pharmacology*
Dose-Response Relationship, Drug
Hypertrophy, Left Ventricular / prevention & control*
Nitric Oxide Synthase Type III / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Rats, Wistar
Receptors, sigma / agonists*,  genetics
Signal Transduction / drug effects
Time Factors
Up-Regulation / drug effects
Reg. No./Substance:
0/Cardiotonic Agents; 0/Receptors, sigma; 0/sigma-1 receptor; 53-43-0/Dehydroepiandrosterone; EC Oxide Synthase Type III; EC Proteins c-akt

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