Oxygen radicals attenuate the contractility of skinned muscle fibres from the pig myocardium.
This study deals with the influence of oxygen radicals on the contraction of skinned muscle fibres from pig myocardium. The radicals were generated by xanthine-xanthine oxidase (X/XO) or by Fe2+/H2O2 (Fenton system). Addition of the X/XO to the incubation medium (KCl/imidazole) induced a depression of the contractility which was dependent from the incubation time and the X/XO concentration. The maximum contraction in the presence of high concentrations of free calcium ions (pCa 4.32) decreased to 52.0 +/- 15.5% (p < 0.01). The EC50 of calcium ions inducing fibre contraction increased from 2.82 +/- 0.66 mumol/l to 5.47 +/- 2.06 mumol/l (p < 0.05). The Hill plot of contraction versus concentration of calcium ions was shifted to the right and the maximum of contractility was attenuated. Replacement of X/XO by the Fenton system was without significant effects on the fibre contractility. Addition of 5.10(-4) mol/l APP 210-533 (3-amino-6-methyl-5-phenyl-1,2- dihydropyrid-2-on), a known "calcium sensitizer", increased the fibre contractility in radical impaired fibres, too. This may indicate that the radicals did not impair the troponine complex. Oxygen radicals were detected by electron spin resonance spectroscopy spin trapping using 5,5-dimethylpyrroline-1-oxide. Superoxide radicals were found in the presence of X/XO whereas addition of Fe2/H2O2 to the incubation medium resulted in the formation of hydroxyl radical adducts. The appearance of additional adducts observed in both system is discussed. The experiments indicate that free radicals can interact with components of the skinned fibre (probably with contractile proteins of the myocardial muscle cells) resulting in an impairment of the contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
Forschungsinstitut für Molekulare Pharmakologie, Forschungsverbund e.V., Berlin.
H
H
Löwe
I
I
Baeger
I E
IE
Blasig
R F
RF
Haseloff
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D011728:Pyridones / Q000494:pharmacology; D013552:Swine
D005609:Free Radicals; D011728:Pyridones; C045982:3-amino-6-methyl-5-phenyl-2(1H)-pyridinone