Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-1
pubmed:abstractText
This study tested the hypothesis that specific hypoxic molecules, including hypoxia-inducible factor-1alpha (HIF-1alpha), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF), are upregulated within the cerebral cortex of acutely anemic rats. Isoflurane-anesthetized rats underwent acute hemodilution by exchanging 50% of their blood volume with pentastarch. Following hemodilution, mean arterial pressure and arterial Pa(O(2)) values did not differ between control and anemic rats while the hemoglobin concentration decreased to 57 +/- 2 g/l. In anemic rats, cerebral cortical HIF-1alpha protein levels were increased, relative to controls (1.7 +/- 0.5-fold, P < 0.05). This increase was associated with an increase in mRNA levels for VEGF, erythropoietin, CXCR4, iNOS, and nNOS (P < 0.05 for all), but not endothelial NOS. Cerebral cortical nNOS and VEGF protein levels were increased in anemic rats, relative to controls (2.0 +/- 0.2- and 1.5 +/- 0.4-fold, respectively, P < 0.05 for both). Immunohistochemistry demonstrated increased HIF-1alpha and VEGF staining in perivascular regions of the anemic cerebral cortex and an increase in the number of nNOS-positive cerebral cortical cells (3.2 +/- 1.0-fold, P < 0.001). The nNOS-positive cells costained with the neuronal marker, Neu-N, but not with the astrocytic marker glial fibrillary acidic protein (GFAP). These nNOS-positive neurons frequently sent axonal projections toward cerebral blood vessels. Conversely, VEGF immunostaining colocalized with both neuronal (NeuN) and astrocytic markers (GFAP). In conclusion, acute normotensive, normoxemic hemodilution increased the levels of HIF-1alpha protein and mRNA for HIF-1-responsive molecules. nNOS and VEGF protein levels were also increased within the cerebral cortex of anemic rats at clinically relevant hemoglobin concentrations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0363-6119
pubmed:author
pubmed:issnType
Print
pubmed:volume
292
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R403-14
pubmed:meshHeading
pubmed-meshheading:16973934-Anemia, pubmed-meshheading:16973934-Animals, pubmed-meshheading:16973934-Blood Pressure, pubmed-meshheading:16973934-Blotting, Western, pubmed-meshheading:16973934-Cerebral Cortex, pubmed-meshheading:16973934-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:16973934-Fluorescent Antibody Technique, pubmed-meshheading:16973934-Glyceraldehyde-3-Phosphate Dehydrogenases, pubmed-meshheading:16973934-Hemodilution, pubmed-meshheading:16973934-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:16973934-Immunohistochemistry, pubmed-meshheading:16973934-Male, pubmed-meshheading:16973934-Nitric Oxide Synthase Type I, pubmed-meshheading:16973934-Oxygen, pubmed-meshheading:16973934-RNA, Messenger, pubmed-meshheading:16973934-Rats, pubmed-meshheading:16973934-Rats, Sprague-Dawley, pubmed-meshheading:16973934-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16973934-Vascular Endothelial Growth Factor A
pubmed:year
2007
pubmed:articleTitle
Increased expression of HIF-1alpha, nNOS, and VEGF in the cerebral cortex of anemic rats.
pubmed:affiliation
Department of Anesthesia, Cara Phelan Trauma Research Centre, University of Toronto, St. Michael's Hospital, 30 Bond St., Toronto, Ontario, M5B 1W8, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't