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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1998-9-10
pubmed:abstractText
The current study was designed to determine the effect of recombinant endothelial nitric oxide synthase (eNOS) gene expression on endothelium-dependent relaxations to bradykinin in isolated canine basilar, coronary, or femoral arteries. Arterial rings were exposed ex vivo (30 minutes at 37 degrees C) to an adenoviral vector encoding either the eNOS gene (AdCMVeNOS) or the beta-galactosidase reporter gene (AdCMVbeta-Gal). Twenty-four hours after transduction, transgene expression was evident mainly in the adventitia. Expression of recombinant proteins was much higher in basilar arteries than in coronary or femoral arteries. Rings of control, AdCMVbeta-Gal, and AdCMVeNOS arteries with and without endothelium were suspended for isometric tension recording. Levels of cGMP were measured by radioimmunoassay. In AdCMVeNOS basilar arteries with endothelium, relaxations to low concentrations of bradykinin (3 x 10(-11) to 10(-9) mol/L) were significantly augmented. In contrast, in coronary and femoral arteries with endothelium, AdCMVeNOS transduction did not affect relaxations to bradykinin. Removal of the endothelium abolished bradykinin-induced relaxations in control and AdCMVbeta-Gal basilar arteries. However, in basilar arteries transduced with AdCMVeNOS even when the endothelium was removed, stimulation with bradykinin (3 x 10(-11) to 10(-9) mol/L) caused relaxations as well as increases in cGMP production. The relaxations to bradykinin were completely blocked by an NOS inhibitor, NG-nitro-L-arginine methyl ester. Electron microscopic analysis revealed that recombinant eNOS protein was expressed in fibroblasts of the basilar artery adventitia. These results suggest that genetically modified adventitial fibroblasts may restore production of NO in cerebral arteries without endothelium. Our findings support a novel concept in vascular biology that fibroblasts in the adventitia may play a role in the regulation of vascular tone after successful transfer and expression of recombinant eNOS gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1079-5642
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1231-41
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9714129-Adenoviridae, pubmed-meshheading:9714129-Animals, pubmed-meshheading:9714129-Arteries, pubmed-meshheading:9714129-Bradykinin, pubmed-meshheading:9714129-Cyclic GMP, pubmed-meshheading:9714129-Dogs, pubmed-meshheading:9714129-Endothelium, Vascular, pubmed-meshheading:9714129-Gene Expression Regulation, Enzymologic, pubmed-meshheading:9714129-Gene Transfer Techniques, pubmed-meshheading:9714129-Genes, Reporter, pubmed-meshheading:9714129-Genetic Vectors, pubmed-meshheading:9714129-Histocytochemistry, pubmed-meshheading:9714129-Humans, pubmed-meshheading:9714129-Microscopy, Electron, pubmed-meshheading:9714129-Nitric Oxide, pubmed-meshheading:9714129-Nitric Oxide Synthase, pubmed-meshheading:9714129-Nitric Oxide Synthase Type III, pubmed-meshheading:9714129-Recombinant Proteins, pubmed-meshheading:9714129-beta-Galactosidase
pubmed:year
1998
pubmed:articleTitle
Adventitial expression of recombinant eNOS gene restores NO production in arteries without endothelium.
pubmed:affiliation
Department of Anesthesiology, Mayo Clinic, Rochester, Minn 55905, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't