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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4 Pt 2
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pubmed:dateCreated |
1996-12-16
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pubmed:abstractText |
The mechanism of the acute negative inotropic effect of tumor necrosis factor-alpha (TNF-alpha) was studied in enzymatically isolated adult rabbit ventricular myocytes. In cells loaded with fura 2 acetoxymethyl ester (AM) and paced intermittently at 0.2 Hz, TNF-alpha at doses < or = 10,000 U/ml caused a significant reduction in active cell shortening at 20 min, without reducing the amplitude of the accompanying intracellular Ca2+ concentration ([Ca2+]i) transient. Similar results were obtained in cells loaded with indo 1-AM and paced continuously at 0.2 Hz during exposure to TNF-alpha (10,000 U/ml). The effect of TNF-alpha on cell shortening could be prevented by the nitric oxide (NO) synthase blocker NG-nitro-L-arginine methyl ester (L-NAME) but not its inactive enantiomer NG-nitro-D-arginine methyl ester (D-NAME). The NO scavenger hemoglobin also attenuated the effects of TNF-alpha. TNF-alpha also caused a significant increase in diastolic cell length without any change in diastolic [Ca2+]i. The effect on cell length was prevented by L-NAME but not D-NAME. In cells loaded with the pH indicator seminaphthorhodafluor-AM, TNF-alpha did not alter pH sufficiently to account for the negative inotropic effect. These data suggest that high doses of TNF-alpha can acutely induce NO synthesis in isolated myocytes and reduce contractility by decreasing myofilament [Ca2+]i responsiveness. The mechanism of this altered myofilament [Ca2+]i response is unknown but does not appear to be pH mediated.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0002-9513
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
271
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
H1449-55
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8897939-Animals,
pubmed-meshheading:8897939-Calcium,
pubmed-meshheading:8897939-Cell Separation,
pubmed-meshheading:8897939-Dose-Response Relationship, Drug,
pubmed-meshheading:8897939-Guinea Pigs,
pubmed-meshheading:8897939-Intracellular Membranes,
pubmed-meshheading:8897939-Myocardial Contraction,
pubmed-meshheading:8897939-Myocardium,
pubmed-meshheading:8897939-Nitric Oxide,
pubmed-meshheading:8897939-Osmolar Concentration,
pubmed-meshheading:8897939-Rabbits,
pubmed-meshheading:8897939-Tumor Necrosis Factor-alpha
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pubmed:year |
1996
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pubmed:articleTitle |
Effects of TNF-alpha on [Ca2+]i and contractility in isolated adult rabbit ventricular myocytes.
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pubmed:affiliation |
Division of Cardiology, School of Medicine, University of California, Los Angeles 90095, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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