| Stimulation of sigma-1 receptor signaling by dehydroepiandrosterone ameliorates pressure overload-induced hypertrophy and dysfunctions in ovariectomized rats. | |
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MedLine Citation:
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PMID: 19769544 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Md Shenuarin Bhuiyan; Kohji Fukunaga |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Expert opinion on therapeutic targets Volume: 13 ISSN: 1744-7631 ISO Abbreviation: Expert Opin. Ther. Targets Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-22 Completed Date: 2009-12-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101127833 Medline TA: Expert Opin Ther Targets Country: England |
Other Details:
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Languages: eng Pagination: 1253-65 Citation Subset: IM |
Affiliation:
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Tohoku University, Graduate School of Pharmaceutical Sciences, Department of Pharmacology, Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects Cardiotonic Agents / administration & dosage, pharmacology* Dehydroepiandrosterone / administration & dosage, pharmacology* Dose-Response Relationship, Drug Female Hypertrophy, Left Ventricular / prevention & control* Nitric Oxide Synthase Type III / metabolism Ovariectomy Proto-Oncogene Proteins c-akt / metabolism Rats Rats, Wistar Receptors, sigma / agonists*, genetics Signal Transduction / drug effects Time Factors Up-Regulation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/Receptors, sigma; 0/sigma-1 receptor; 53-43-0/Dehydroepiandrosterone; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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