Studies on the role of superoxide anion radicals for the cardiotoxicity of adrenochrome.
Adrenochrome is an oxidative product of adrenaline and possesses cardiotoxic properties. As oxygen free radicals play a role in the cytotoxic effects of catecholamines, the role of superoxide anion radicals, as mediators of adrenochrome toxicity, was investigated using electrically-driven Langendorff rabbit hearts with depleted catecholamine stores. Repetitive regional myocardial ischemia (MI) was induced by coronary artery branch ligature, and MI was quantitated from epicardial NADH-fluorescence photography. Adrenochrome (10(-6) mol/l) was added to the perfusion solution after a reperfusion period of 20 min, 30 min before the 2nd coronary occlusion, with or without the additional application of SOD (30 U/ml). Left ventricular pressure was significantly enhanced by adrenochrome (p < 0.05), but it fell rapidly down below its initial value (p < 0.05). Coronary flow was significantly decreased by adrenochrome (p < 0.05). Whereas epicardial NADH-fluorescence was similar after repetitive coronary occlusions in untreated controls, it was significantly enhanced by adrenochrome (p < 0.05). The deleterious effects of adrenochrome on MI were not inhibited by SOD. Thus, there is no evidence for superoxide anion radicals as mediators of the deleterious effects of adrenochrome on MI in isolated rabbit hearts. The deleterious effects of adrenochrome on MI in isolated rabbit hearts might be caused by functional effects, impairing the oxygen consumption/oxygen supply balance.
Rump
A F
AF
Institut für Pharmakologie, Universität Köln, Cologne, Germany.
Schierholz
J
J
Rösen
R
R
Güttler
K
K
Klaus
W
W
D000323:Adrenochrome / Q000633:toxicity*; D000818:Animals; D003326:Coronary Circulation; D004837:Epinephrine / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008856:Microscopy, Fluorescence; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010496:Pericardium / Q000473:pathology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000737:chemistry; D013481:Superoxides / Q000378:metabolism*; D016277:Ventricular Function, Left
D009243:NAD; D013481:Superoxides; D000323:Adrenochrome; D013482:Superoxide Dismutase; D004837:Epinephrine