Linked Life Data

17827917

Source:http://linkedlifedata.com/resource/pubmed/id/17827917

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-9-10
pubmed:abstractText
The nitric oxide (NO) synthases (NOSs) system consists of three different isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOSs (eNOS). The roles of NO in vivo have been extensively investigated in pharmacological studies with NOS inhibitors and in studies with mice lacking each NOS isoform. However, in the pharmacological studies, the specificity of NOS inhibitors continues to be an issue of debate, while in the studies with mice lacking each NOS isoform, compensatory mechanism by other NOSs appears to be involved. Thus, the ultimate roles of endogenous NO in our body still remain to be fully elucidated. To address this important issue, we have successfully developed mice in which all three NOS genes are completely disrupted. NOS expression and activities were totally absent in the triply n/i/eNOS(-/-) mice before and after treatment with lipopolysaccharide. While the triply n/i/eNOS(-/-) mice were viable, their survival and fertility rates were markedly reduced as compared with wild-type mice. The first noticeable phenotypes were polyuria, polydipsia, and renal unresponsiveness to vasopressin, characteristics consistent with nephrogenic diabetes insipidus. We subsequently observed that in those mice, arteriosclerosis is spontaneously developed with a clustering of cardiovascular risk factors. These results provide the first evidence that genetic disruption of all three NOSs causes a variety of cardiovascular diseases in mice in vivo, demonstrating the critical role of the endogenous NOSs system in maintaining cardiovascular homeostasis.
pubmed:language
jpn
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0031-6903
pubmed:author
pubmed:issnType
Print
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1347-55
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
[Development of genetically engineered mice lacking all three nitric oxide synthase isoforms].
pubmed:affiliation
Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Kitakyushu, Japan. mt2498@med.uoeh-u.ac.jp
pubmed:publicationType
Journal Article, English Abstract, Review, Research Support, Non-U.S. Gov't