Linked Life Data

21173341

Source:http://linkedlifedata.com/resource/pubmed/id/21173341

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-20
pubmed:abstractText
Renovascular hypertension in mice is characterized by an elevation in hypothalamic angiotensin II levels. The paraventricular nucleus (PVN) is a major cardioregulatory site implicated in the neurogenic component of renovascular hypertension. Increased superoxide (O(2)(-·)) production in the PVN is involved in angiotensin II-dependent neurocardiovascular diseases such as hypertension and heart failure. Here, we tested the hypothesis that excessive O(2)(-·) production and activation of the redox-regulated transcription factor activator protein-1 (AP-1) in PVN contributes to the development and maintenance of renovascular hypertension. Male C57BL/6 mice underwent implantation of radiotelemeters, bilateral PVN injections of an adenovirus (Ad) encoding superoxide dismutase (AdCuZnSOD) or a control gene (LacZ), and unilateral renal artery clipping (2-kidney, one-clip [2K1C]) or sham surgery. AP-1 activity was longitudinally monitored in vivo by bioluminescence imaging in 2K1C or sham mice that had undergone PVN-targeted microinjections of an Ad encoding the firefly luciferase (Luc) gene downstream of AP-1 response elements (AdAP-1Luc). 2K1C evoked chronic hypertension and an increase in O(2)(-·) production in the PVN. Viral delivery of CuZnSOD to the PVN not only prevented the elevation in O(2)(-·) but also abolished renovascular hypertension. 2K1C also caused a surge in AP-1 activity in the PVN, which paralleled the rise in O(2)(-·) production in this brain region, and this was prevented by treatment with AdCuZnSOD. Finally, Ad-mediated expression of a dominant-negative inhibitor of AP-1 activity in the PVN prevented 2K1C-evoked hypertension. These results implicate oxidant signaling and AP-1 transcriptional activity in the PVN as key mediators in the pathogenesis of renovascular hypertension.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
289-97
pubmed:dateRevised
2011-5-5
pubmed:meshHeading
pubmed-meshheading:21173341-Adenoviridae, pubmed-meshheading:21173341-Animals, pubmed-meshheading:21173341-Atrophy, pubmed-meshheading:21173341-Blood Pressure, pubmed-meshheading:21173341-Heart Rate, pubmed-meshheading:21173341-Hypertension, Renovascular, pubmed-meshheading:21173341-Immunohistochemistry, pubmed-meshheading:21173341-Kidney, pubmed-meshheading:21173341-Luciferases, pubmed-meshheading:21173341-Luminescent Measurements, pubmed-meshheading:21173341-Male, pubmed-meshheading:21173341-Mice, pubmed-meshheading:21173341-Mice, Inbred C57BL, pubmed-meshheading:21173341-Organ Size, pubmed-meshheading:21173341-Oxidation-Reduction, pubmed-meshheading:21173341-Paraventricular Hypothalamic Nucleus, pubmed-meshheading:21173341-Reactive Oxygen Species, pubmed-meshheading:21173341-Superoxide Dismutase, pubmed-meshheading:21173341-Superoxides, pubmed-meshheading:21173341-Transcription Factor AP-1
pubmed:year
2011
pubmed:articleTitle
In vivo bioluminescence imaging reveals redox-regulated activator protein-1 activation in paraventricular nucleus of mice with renovascular hypertension.
pubmed:affiliation
Biomedical Sciences, College of Veterinary Medicine, Weill Cornell Medical College, Cornell University, Ithaca, NY 14853-6401, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural