Propranolol reduces anoxia/reoxygenation-mediated injury of adult myocytes through an anti-radical mechanism.
The effects of propranolol (PRO) and atenolol (ATE) on adult canine myocytes exposed to 30 min anoxia (A:95% N2/5% CO2) and subsequent reoxygenation (R:95% O2/5% CO2) for up to 20 min was investigated. In some studies, comparison of effects were made with that of superoxide dismutase (SOD). Although anoxia alone produced only minimal injury, reoxygenation in the absence of the beta-blockers or SOD was associated with significant losses of cellular viability, elevated release of cellular lactate dehydrogenase, and increased formation of lipid peroxidation products. Myocytes exposed to A/R in the presence of d,1-PRO (20, 200 microM) were afforded substantial, concentration-dependent protection during 20 min reoxygenation. Significant protection was also observed in the presence of 2 microM d-PRO (non-active beta-blocker), but only after a longer preincubation period (2 h). SOD (10 micrograms/ml) provided equi-potent protection to that of 200 microM d,1-PRO. By contrast, the more water-soluble beta-blocker, ATE (200 microM), offered only minor protection. Electron Spin Resonance spin trapping studies using alpha-phenyl-tert-butylnitrone (PBN) were also performed with A/R myocytes in the presence or absence of drug treatment. Short-term (10 min) exposure to d,1-PRO (200 microM) prior to A/R, or to SOD, resulted in a 71-84% reduction in total PBN lipid radical adduct formation (alkoxyl; alpha H = 2.0-2.5 G, alpha N = 13.5-13.75 G); long-term exposure (2 h) to 2 microM d-PRO resulted in a 51% reduction. These data suggest that the superoxide anion was an initiator of events leading to subsequent lipid radical formation and that the anti-peroxidative properties of PRO appear to be independent of beta-receptor blockade.
Kramer
J H
JH
Department of Medicine, George Washington University Medical Center, Washington, D.C. 20037.
Mak
I T
IT
Freedman
A M
AM
Weglicki
W B
WB
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D004285:Dogs; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D011433:Propranolol / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D005609:Free Radicals; D008315:Malondialdehyde; D001262:Atenolol; D011433:Propranolol; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D010100:Oxygen