| Oral intake of rosiglitazone promotes a central antihypertensive effect via upregulation of peroxisome proliferator-activated receptor-gamma and alleviation of oxidative stress in rostral ventrolateral medulla of spontaneously hypertensive rats. | |
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MedLine Citation:
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PMID: 20404217 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rosiglitazone, a synthetic ligand of transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma), possesses a blood pressure-lowering effect beyond insulin sensitizing and glucose lowering. Oxidative stress in rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons for the maintenance of neurogenic vasomotor tone are located, contributes to neural mechanisms of hypertension. Activation of PPAR-gamma protects against oxidative stress in RVLM by upregulation of mitochondrial uncoupling protein 2 (UCP2). We tested the hypothesis that oral intake of rosiglitazone exerts a central antihypertensive effect by ameliorating oxidative stress in RVLM via transcriptional upregulation of UCP2 after PPAR-gamma activation. In adult spontaneously hypertensive rats but not normotensive Wistar-Kyoto rats, oral intake of rosiglitazone for 1 week resulted in vasodepression and a reduction in the vasomotor components of the systemic arterial pressure spectrum, our experimental index for sympathetic vasomotor tone. These antihypertensive effects of rosiglitazone in spontaneously hypertensive rats were abrogated by microinjection bilaterally into RVLM of PPAR-gamma small interfering RNA. Oral intake of rosiglitazone also upregulated UCP2 and ameliorated the heightened superoxide anion level in RVLM of spontaneously hypertensive rats. Protection against oxidative stress in RVLM by rosiglitazone was abrogated by PPAR-gamma small interfering RNA or by antisense oligonucleotide against ucp2 mRNA. Gene knockdown of ucp2 in RVLM also reversed the antihypertensive effect of rosiglitazone. These results suggest that oral intake of rosiglitazone promotes a central antihypertensive effect by decreasing sympathetic vasomotor activity through a PPAR-gamma-dependent protection against oxidative stress in RVLM via transcriptional upregulation of the mitochondrial UCP2. |
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Authors:
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Samuel H H Chan; Kay L H Wu; Peter S S Kung; Julie Y H Chan |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-19 |
Journal Detail:
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Title: Hypertension Volume: 55 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-06-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 1444-53 Citation Subset: IM |
Affiliation:
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Center for Translation Research in Biomedical Sciences, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan, Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Amlodipine / pharmacology Analysis of Variance Animals Blood Pressure / drug effects, physiology Disease Models, Animal Heart Rate / drug effects, physiology Hypertension / drug therapy, physiopathology* Kidney Medulla / drug effects, physiology Male Oxidative Stress / drug effects*, physiology PPAR gamma / drug effects*, genetics*, metabolism Probability RNA, Messenger / metabolism Random Allocation Rats Rats, Inbred SHR Rats, Inbred WKY Reverse Transcriptase Polymerase Chain Reaction Thiazolidinediones / pharmacology* Up-Regulation Vasodilator Agents / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/PPAR gamma; 0/RNA, Messenger; 0/Thiazolidinediones; 0/Vasodilator Agents; 122320-73-4/rosiglitazone; 88150-42-9/Amlodipine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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