Miller, D. J. and MacFarlane, N. G. (1995) Intracellular effects of free radicals and reactive oxygen species in cardiac muscle. Journal of Human Hypertension, 9(6), pp. 465-73. (PMID:7473529)
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Abstract
Oxygen-derived free radicals (FRs) and other reactive oxygen species (ROS) have been implicated in the deleterious aspects of myocardial infarction, neutrophil infiltration and post-ischaemic reperfusion. We studied their actions on the main intracellular organelles of Ca-compartmentation and force production (the sarcoplasmic reticulum (SR) and myofilaments) in rat heart preparations by using two forms of chemical 'skinning'. We recorded Ca(2+)-activated isometric tension or, in saponin-treated trabeculae where SR function is maintained, either tension alone or tension and [Ca2+] transients evoked by caffeine. A single, brief application of xanthine/xanthine oxidase (generating superoxide; O2-) rapidly and irreversibly inhibits Ca(2+)-activated force with a dose- and time-dependent action. The kinetics of residual force production are slowed. Rigor induction (by ATP withdrawal) before and during exposure to .O2- prevents this action, suggesting the .O2(-)-sensitive site is occluded in rigor. Myofilament Ca-sensitivity and SR function were unaffected by .O2- or physiologically relevant [H2O2] (< 10 microM). Briefly applying 10-50 microM hypochlorous acid (HOCl) increased Ca-sensitivity and resting tension, but reduced Ca-activated force, in a manner consistent with 'rigor-like' crossbridges being involved. HOCl also provoked spontaneous Ca-release but reduced net SR Ca-uptake. Electron microscopy reveals that the myofilament lattice suffers a characteristic disruption by HOCl but not by .O2-. We conclude that FRs and ROS associated with myocyte dysfunction, reperfusion and inflammation could contribute to post-ischaemic myocardial dysfunction.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Miller, Dr David and MacFarlane, Professor Niall |
Authors: | Miller, D. J., and MacFarlane, N. G. |
College/School: | College of Medical Veterinary and Life Sciences > School of Life Sciences |
Journal Name: | Journal of Human Hypertension |
ISSN: | 0950-9240 |
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