Effect of in vivo heart irradiation on coronary reactivity in the rat.
The frequent exposure of the heart to radiation during thoracic tumor radiotherapy often results in chronic impairment of myocardial function. The aim of the present investigation was to evaluate the effect of irradiation on coronary vascular tone in rat hearts exposed in vivo to a single dose of 20 Gy gamma rays. The ability of rat hearts to respond to changes in coronary reactivity was analyzed 1, 15, 30 and 60 days following cardiac irradiation, using the Langendorff model, after perfusion of either L-nitro-arginine (LNA), an inhibitor of nitric oxide synthetase or SIN 1, a nitric oxide donor drug. LNA-induced vasoconstriction and SIN 1-induced vasodilation were lost respectively 15 days and 30 days after irradiation, and associated with smooth muscle cell alterations observed in microscopy, but without any changes in myocardial MDA levels. Thus, our results suggest that 1) endothelium may represent an early and specific radiation target, characterized by radiation-induced vascular tone dysfunctions, with no detectable microscopical changes; 2) alterations are progressive, resulting first from endothelial damage, followed by smooth muscle cell injuries. In conclusion, a local cardiac irradiation induced cellular dysfunction, characterized by a loss of coronary reactivity without changes of the lipid peroxidation index in the hearts.
Laboratoire de Physiopathologie et de Pharmacologie Cardiovasculaires Expérimentales, IFR Santé N(o)100, Faculté de Médecine, Dijon, France. Florence.Bouyer@u-bourgogne.fr
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Bouyer-Dalloz
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Maingon
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Benderitter
J L
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Connat
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Cottin
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Briot
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Rochette
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000528:radiation effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000528:radiation effects*; D015227:Lipid Peroxidation / Q000528:radiation effects; D008297:Male; D009129:Muscle Tonus / Q000528:radiation effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat