| Down-regulation of DDAH2 and eNOS induces endothelial dysfunction in sinoaortic-denervated rats. | |
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MedLine Citation:
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PMID: 21549701 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The aim of present study was to investigate whether downregulation of dimethylarginine dimethylaminohydrolase (DDAH2) and endothelial nitric oxide synthase (eNOS) induced endothelial dysfunction in sinoaortic-denervated (SAD) rats. SAD rats exhibited significantly higher blood pressure (BP) variability and markedly lower baroreflex sensitivity. However, there was no significant difference in BP between SAD rats and sham-operated rats. In SAD rats, ultrastructural analysis revealed that endothelial cells were degenerated and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) study showed that apoptotic aortic endothelial cells increased. Circulating angiotensinII (AngII), asymmetric dimethylarginine (ADMA) and malondialdehyde (MDA) levels in SAD rats were similar to sham-operated rats, but aortic AngII and MDA levels locally increased. Endothelium-mediated relaxation of thoracic aorta isolated from SAD rats was impaired compared to sham-operated rats, whereas the sodium nitroprusside-induced relaxation was quite similar. Western blotting results showed that DDAH2 and eNOS expressions decreased significantly in the aortae of SAD rats. Treatment of primary cultured rat aortic endothelial cells with AngII (1μM) resulted in a marked reduction of DDAH2 and eNOS expressions, and coadministration of losartan (1μM), an AT(1) receptor antagonist, abolished the effect. In conclusion, downregulation of DDAH2 and eNOS induced endothelial dysfunction in SAD rats. DDAH2 and eNOS may be the potential targets for treatment of endothelial dysfunction. |
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Authors:
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Feng Jinzhong; Luo Hede; Qiu Yihua; Zhou Wei; Yu Feng; Wu Feng |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-28 |
Journal Detail:
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Title: European journal of pharmacology Volume: - ISSN: 1879-0712 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-5-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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