Linked Life Data

11788458

Source:http://linkedlifedata.com/resource/pubmed/id/11788458

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-1-14
pubmed:abstractText
Previous in vitro experiments have shown that hyperhomocysteinemia leads to oxidative inactivation of nitric oxide, in part by inhibiting the expression of cellular glutathione peroxidase (GPx-1). To elucidate the role of intracellular redox status on homocysteine-induced endothelial dysfunction and oxidant stress, heterozygous cystathionine beta-synthase-deficient (CBS(-/+)) and wild-type (CBS(+/+)) mice were treated with the cysteine donor L-2-oxothiazolidine-4-carboxylic acid (OTC). CBS(-/+) mice had significantly lower GPx-1 activity compared with their CBS(+/+) littermates, and OTC treatment led to a modest increase in tissue GPx-1 activity and significant increases in total thiols and in reduced glutathione levels in both CBS(+/+) and CBS(-/+) mice. Superfusion of the mesentery with beta-methacholine or bradykinin produced dose-dependent vasodilation of mesenteric arterioles in CBS(+/+) mice and in CBS(+/+) mice treated with OTC. In contrast, mesenteric arterioles from CBS(-/+) mice manifested dose-dependent vasoconstriction in response to both agonists. OTC treatment of CBS(-/+) mice restored normal microvascular vasodilator reactivity to beta-methacholine and bradykinin. These findings demonstrate that mild hyperhomocysteinemia leads to endothelial dysfunction in association with decreased bioavailable nitric oxide. Increasing the cellular thiol and reduced glutathione pools and increasing GPx-1 activity restores endothelial function. These findings emphasize the importance of intracellular redox balance for nitric oxide bioactivity and endothelial function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1524-4636
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34-41
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11788458-Animals, pubmed-meshheading:11788458-Bradykinin, pubmed-meshheading:11788458-Cystathionine beta-Synthase, pubmed-meshheading:11788458-Dose-Response Relationship, Drug, pubmed-meshheading:11788458-Endothelium, Vascular, pubmed-meshheading:11788458-Glutathione Peroxidase, pubmed-meshheading:11788458-Homocysteine, pubmed-meshheading:11788458-Hyperhomocysteinemia, pubmed-meshheading:11788458-Liver, pubmed-meshheading:11788458-Mesentery, pubmed-meshheading:11788458-Methacholine Chloride, pubmed-meshheading:11788458-Mice, pubmed-meshheading:11788458-Nitric Oxide, pubmed-meshheading:11788458-Oxidation-Reduction, pubmed-meshheading:11788458-Oxidative Stress, pubmed-meshheading:11788458-Pyrrolidonecarboxylic Acid, pubmed-meshheading:11788458-Sulfhydryl Compounds, pubmed-meshheading:11788458-Thiazoles, pubmed-meshheading:11788458-Thiazolidines, pubmed-meshheading:11788458-Vasodilation
pubmed:year
2002
pubmed:articleTitle
Cellular redox state and endothelial dysfunction in mildly hyperhomocysteinemic cystathionine beta-synthase-deficient mice.
pubmed:affiliation
Whitaker Cardiovascular Institute, Evans Department of Medicine, Boston University School of Medicine, Boston, MA 02118-2394, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't