Lack of inhibition of endothelial nitric oxide synthase in the isolated rat aorta by doxorubicin.
Besides inducing cardiotoxicity, doxorubicin also affects the vasculature. Recent observations in cultured endothelial cells indicated that the endothelial form of nitric oxide synthase might be inhibited by doxorubicin thereby seriously interfering with vascular function. We have investigated the effect of doxorubicin on the relaxation induced by the muscarinic agonist carbachol in the isolated rat aorta. It was found that doxorubicin at concentrations up to 50 microM does not alter the relaxant response to carbachol. Direct measurement of nitrite, the metabolite of NO*, by the Griess assay confirmed our observation that NO*)production is not inhibited by doxorubicin.
den Hartog
G J M
GJ
Department of Pharmacology and Toxicology, University Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands. gi.denhartog@farmaco.unimaas.nl
Boots
A W
AW
Haenen
G R M M
GR
van der Vijgh
W J F
WJ
Bast
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D018679:Cholinergic Agonists; D009569:Nitric Oxide; D004317:Doxorubicin; D002217:Carbachol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat