Rapid-onset endothelial dysfunction with adriamycin: evidence for a dysfunctional nitric oxide synthase

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 ·-)...

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Published in:Vascular medicine (London, England) England), 2003-05, Vol.8 (2), p.101-107
Main Authors: Duquaine, Damon, Hirsch, Glenn A, Chakrabarti, Anjan, Han, Zhenguo, Kehrer, Chris, Brook, Robert, Joseph, Joy, Schott, Anne, Kalyanaraman, B, Vasquez-Vivar, Jeanette, Rajagopalan, Sanjay
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brachial Artery
Doxorubicin - metabolism
Doxorubicin - toxicity
Drug toxicity and drugs side effects treatment
Electron Spin Resonance Spectroscopy
Endothelium, Vascular - enzymology
Endothelium, Vascular - metabolism
Female
Free Radicals
Humans
Male
Medical sciences
Middle Aged
Nitric Oxide - metabolism
Nitric Oxide Synthase - metabolism
Pharmacology. Drug treatments
Rabbits
Toxicity: cardiovascular system
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Summary: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
ISSN:1358-836X
1358-863X
1477-0377
DOI:10.1191/1358863x03vm476oa