Linked Life Data

12907425

Source:http://linkedlifedata.com/resource/pubmed/id/12907425

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-11-17
pubmed:abstractText
Increased nitric oxide (NO) production by inducible NO synthase (NOS2), an obligate homodimer, is implicated in the cardiovascular sequelae of sepsis. We tested the ability of a highly selective NOS2 dimerization inhibitor (BBS-2) to prevent endotoxin-induced systemic hypotension, myocardial dysfunction, and impaired hypoxic pulmonary vasoconstriction (HPV) in mice. Mice were challenged with Escherichia coli endotoxin before treatment with BBS-2 or vehicle. Systemic blood pressure was measured before and 4 and 7 h after endotoxin challenge, and echocardiographic parameters of myocardial function were measured before and 7 h after endotoxin challenge. The pulmonary vasoconstrictor response to left mainstem bronchus occlusion, which is a measure of HPV, was studied 22 h after endotoxin challenge. BBS-2 treatment alone did not alter baseline hemodynamics. BBS-2 treatment blocked NOS2 dimerization and completely inhibited the endotoxin-induced increase of plasma nitrate and nitrite levels. Treatment with BBS-2 after endotoxin administration prevented systemic hypotension and attenuated myocardial dysfunction. BBS-2 also prevented endotoxin-induced impairment of HPV. In contrast, treatment with NG-nitro-l-arginine methyl ester, which is an inhibitor of all three NOS isoforms, prevented the systemic hypotension but further aggravated the myocardial dysfunction associated with endotoxin challenge. Treatment with BBS-2 prevented endotoxin from causing key features of cardiovascular dysfunction in endotoxemic mice. Selective inhibition of NOS2 dimerization with BBS-2, while sparing the activities of other NOS isoforms, may prove to be a useful treatment strategy in sepsis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2524-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12907425-Animals, pubmed-meshheading:12907425-Aorta, pubmed-meshheading:12907425-Dimerization, pubmed-meshheading:12907425-Endotoxemia, pubmed-meshheading:12907425-Enzyme Inhibitors, pubmed-meshheading:12907425-Gene Expression Regulation, Enzymologic, pubmed-meshheading:12907425-Heart Diseases, pubmed-meshheading:12907425-Hypotension, pubmed-meshheading:12907425-Male, pubmed-meshheading:12907425-Mice, pubmed-meshheading:12907425-Mice, Inbred C57BL, pubmed-meshheading:12907425-Mice, Mutant Strains, pubmed-meshheading:12907425-Nitric Oxide Synthase, pubmed-meshheading:12907425-Nitric Oxide Synthase Type II, pubmed-meshheading:12907425-Nitric Oxide Synthase Type III, pubmed-meshheading:12907425-Nitrites, pubmed-meshheading:12907425-Pulmonary Circulation, pubmed-meshheading:12907425-Vasoconstriction, pubmed-meshheading:12907425-Vasodilation
pubmed:year
2003
pubmed:articleTitle
A selective inducible NOS dimerization inhibitor prevents systemic, cardiac, and pulmonary hemodynamic dysfunction in endotoxemic mice.
pubmed:affiliation
Department of Anesthesia and Critical Care and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114-2620, USA. ichinose@etherdome.mgh.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.