Source:http://linkedlifedata.com/resource/pubmed/id/14518612
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
2003-10-1
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| pubmed:abstractText |
Adriamycin (ADR) is a commonly used chemotherapeutic agent that is believed to exert its effects through the generation of oxygen free radicals. We hypothesized that administration of a single dose of ADR results in endothelial nitric oxide synthase (eNOS)-dependent generation of superoxide (O2*-) and acute endothelial dysfunction. A single dose of ADR (10 mg/kg i.v.) administered to rabbits resulted in rapid attenuation of agonist-dependent responses to acetylcholine and calcium ionophore (A23187). In vitro exposure of ring segments to ADR for < 30 min resulted in O2*- generation measured by electron spin resonance (ESR) with the spin trap segments 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO) that was abolished by endothelial denudation and incubation with diphenyliodonium (DPI) (10 microM) but not L-NMMA (10 microM). Brachial artery flow-mediated dilation (FMD) in patients undergoing chemotherapy with ADR was markedly attenuated after a single dose of ADR (6.5 +/- 1.0 to 2.5 +/- 1.1% (p = 0.0004, time to end of infusion 27 +/- 8 min) while endothelial-independent dilatation with nitroglycerin was unchanged (16.3 +/- 3.1 and 14.33 +/- 2.1% respectively, p = 0.36). Serum nitrite and nitrate concentrations fell from 50 +/- 6 micromol/l pre-ADR to 33 +/- 6 micromol/l post-ADR infusion (p = 0.0005) while serum concentrations of CD141 thrombomodulin and von Willebrand factor (vWF) activity remained unchanged after ADR infusion (36 +/- 13 to 52 +/- 22% ng/ml versus 3.25 +/- 0.98 to 3.01 +/- 0.91%, respectively, p = NS for pre versus post for both). Doppler indices of diastolic function (IVRT, DT and E/A ratios) were not altered in response to ADR. In conclusion, ADR administration results in rapid depletion of systemic NO* levels and attenuation of agonist-dependent responses in rabbits and flow-mediated dilation in the brachial artery of humans. ESR measurements in rabbit ring suggest an endothelial origin for radical production via flavin-containing oxido-reductases such as eNOS or NADPH cytochrome P450 reductase. These findings may have implications for cardiovascular complications noted with ADR.
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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
|
| pubmed:month |
May
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| pubmed:issn |
1358-863X
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| pubmed:author |
pubmed-author:BrookRobertR,
pubmed-author:ChakrabartiAnjanA,
pubmed-author:DuquaineDamonD,
pubmed-author:HanZhenguoZ,
pubmed-author:HirschGlenn AGA,
pubmed-author:JosephJoyJ,
pubmed-author:KalyanaramanBB,
pubmed-author:KehrerChrisC,
pubmed-author:RajagopalanSanjayS,
pubmed-author:SchottAnneA,
pubmed-author:Vasquez-VivarJeanetteJ
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| pubmed:issnType |
Print
|
| pubmed:volume |
8
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
101-7
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:14518612-Animals,
pubmed-meshheading:14518612-Brachial Artery,
pubmed-meshheading:14518612-Doxorubicin,
pubmed-meshheading:14518612-Electron Spin Resonance Spectroscopy,
pubmed-meshheading:14518612-Endothelium, Vascular,
pubmed-meshheading:14518612-Female,
pubmed-meshheading:14518612-Free Radicals,
pubmed-meshheading:14518612-Humans,
pubmed-meshheading:14518612-Male,
pubmed-meshheading:14518612-Middle Aged,
pubmed-meshheading:14518612-Nitric Oxide,
pubmed-meshheading:14518612-Nitric Oxide Synthase,
pubmed-meshheading:14518612-Rabbits
|
| pubmed:year |
2003
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| pubmed:articleTitle |
Rapid-onset endothelial dysfunction with adriamycin: evidence for a dysfunctional nitric oxide synthase.
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| pubmed:affiliation |
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|