Evidence for norepinephrine cardiotoxicity mediated by superoxide anion radicals in isolated rabbit hearts.
Catecholamines have been demonstrated to be cardiotoxic. Besides hemodynamic alterations, oxygen free radicals generated by the auto-oxidation of catecholamines might contribute to their deleterious effects. We examined the influence of exogenous norepinephrine (NE), after inhibiting functional alterations by alpha and beta-adrenoceptor blockade, on acute regional ischemia (MI).


METHODS
We used isolated electrically-driven rabbit hearts with depleted catecholamine stores (reserpine 7.0 mg/kg i.p. 16-24 h before preparation, Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l, 37 degrees C, 185-200 beats/min). Repetitive MI, separated by a reperfusion period of 50 min, was induced by coronary artery branch ligature and quantitated from epicardial NADH-fluorescence photography. Starting after a reperfusion period of 20 min, isolated hearts were treated with NE (10(-6) M), in the presence of propranolol (10(-6) M), phentolamine (10(-6) M) and vitamin C (3 x 10(-8) M) in the perfusion buffer to prevent the functional effects of NE. The influence of the free radical scavenger superoxide dismutase (SOD) (30 U/ml) or captopril (10(-6) M) on MI was also examined.


RESULTS
Left ventricular pressure or coronary flow were not significantly affected by either treatment (p > 0.05). Epicardial NADH-fluorescence area and intensity were, however, significantly enhanced by NE (+22%) (P < 0.05), although propranolol, phentolamine and vitamin C had no significant influence on MI (P > 0.05). SOD had no significant effect on MI in control hearts (P > 0.05) but completely prevented MI enlargement by NE (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Rump
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AF
Institut für Pharmakologie, Universität Köln, Germany.
Klaus
W
W
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D005453:Fluorescence; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D009243:NAD; D009638:Norepinephrine / Q000378:metabolism / Q000633:toxicity*; D010084:Oxidation-Reduction; D011817:Rabbits; D013481:Superoxides / Q000633:toxicity*; D014439:Tyramine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D005609:Free Radicals; D009243:NAD; D013481:Superoxides; D009638:Norepinephrine; D014439:Tyramine