Linked Life Data

2817583

Source:http://linkedlifedata.com/resource/pubmed/id/2817583

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1989-12-11
pubmed:abstractText
Lipoxygenase metabolites of arachidonic acid have been proposed as possible mediators of hypoxic pulmonary vasoconstriction (HPV) in the rat. Since reduced glutathione (GSH) is a required substrate for the synthesis of the sulfidopeptide eicosanoid leukotriene C4 (LTC4), we reasoned that this specific GSH dependence of LTC4 synthesis might allow us to distinguish between the roles of sulfidopeptide leukotrienes and other 5-lipoxygenase metabolites of arachidonic acid. In the present study we have examined the effect of in vivo pretreatment with the GSH synthesis inhibitor buthionine sulfoximine (BSO) on both the hypoxic pressor response and lung leukotriene synthesis in the rat. The intraperitoneal administration of 4 mmol/kg of BSO 30, 20, and 4 h prior to lung excision significantly depleted total lung glutathione as compared to saline-pretreated controls. This depletion of glutathione was associated with a significant attenuation of HPV in isolated perfused lungs but no alteration in pressor response to angiotensin II or KCl. In addition, hypoxia-associated LTC4 levels in lung homogenates were significantly lower in animals pretreated with BSO than in saline-pretreated controls. The specificity of the effects of BSO on lung leukotriene synthesis was examined by quantitating immunoreactive leukotrienes produced by unstimulated and ionophore A23187-stimulated parenchymal lung fragments, lonophore stimulation of lung fragments from BSO-pretreated rats produced 76 +/- 12.2% as much LTC4 and 127 +/- 22.3% as much leukotriene B4 as did fragments from saline-pretreated rats. Our data demonstrating that GSH depletion caused parallel reductions in both HPV and hypoxia-associated lung LTC4 levels are therefore consistent with the hypothesis that sulfidopeptide leukotrienes are involved in this pressor response in the rat.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0003-0805
pubmed:author
pubmed:issnType
Print
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1210-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Inhibition of rat lung glutathione synthesis attenuates hypoxic pulmonary vasoconstriction and the associated leukotriene C4 production.
pubmed:affiliation
Pulmonary and Critical Care Medicine Division, University of Michigan Medical Center, Ann Arbor 48109-0360.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't