Studies of the toxic effects of norepinephrine on isolated cardiomyocytes of guinea-pigs.
Catecholamines have been demonstrated to possess direct cardiotoxic effects mediated by oxygen free radicals in isolated organ preparations. In order to assess direct cytotoxic properties, the influence of exogenous noradrenaline (norepinephrine, CAS 51-41-2) (10(-6) mol/l) on isolated guinea-pigs cardiomyocytes was examined, in the presence of propranolol (10(-6) mol/l) and phentolamine (10(-6) mol/l) to inhibit adrenoceptor-mediated effects. Cell viability was assessed by morphologic examination (% of striated, rod-shaped cells), before and after a treatment period of 15 and 60 min by the measurement of intracellular enzyme activities in the supernatant of the suspension (lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase). The proportion of viable, rod-shaped cardiomyocytes (21.6% +/- 7.6% after preparation, before starting the treatments) significantly decreased over the experimental time (p < 0.05) and, concomitantly, the activity of intracellular enzymes in the supernatant increased. There was no difference between controls and treated suspensions. Thus, there is no evidence for direct toxic effects of norepinephrine in micromolar concentration on isolated cardiomyocytes of guinea-pigs. However, cytoprotective effects by propranolol and/or phentolamine cannot be excluded in this model.
Rump
A F
AF
Institut für Pharmakologie, Universität Köln, Cologne, Germany.
Schierholz
J
J
Biederbick
W
W
Koch
A E
AE
Klaus
W
W
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D009638:Norepinephrine / Q000633:toxicity*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D009638:Norepinephrine; D010646:Phentolamine