Blockade of platelet-mediated relaxation in rat aortic rings exposed to xanthine-xanthine oxidase

1994 ◽  
Vol 266 (6) ◽  
pp. H2212-H2219 ◽  
Author(s):  
B. C. Yang ◽  
S. Khan ◽  
J. L. Mehta
Keyword(s):  
Free Radicals ◽  
Xanthine Oxidase ◽  
Hydroxyl Radicals ◽  
Vascular Tone ◽  
Oxygen Free Radicals ◽  
Ischemia Reperfusion ◽  
Arterial Occlusion ◽  
Superoxide Anions ◽  
Vascular Tissues ◽  
Hydroxyl Radical Scavengers

Platelet-induced relaxation of endothelium-intact vascular tissues, mediated via release of endothelium-derived relaxing factor (EDRF), is diminished or lost after ischemia and reperfusion. Release of oxygen free radicals during ischemia-reperfusion may degrade EDRF and influence response of vascular tissues to platelets. To determine platelet modulation of tone of blood vessels treated with oxygen free radicals, rat aortic rings with intact endothelium were exposed to xanthine (X) plus xanthine oxidase (XO) 5 min before contraction with norepinephrine followed by exposure of rings to platelets. Treatment of aortic rings with X+XO caused a modest contraction, potentiated norepinephrine-mediated contraction, and inhibited platelet-mediated vasorelaxation. Exposure of aortic rings to X+XO also decreased ADP- as well as acetylcholine-mediated relaxation. Pretreatment of rings with superoxide dismutase or catalase did not change X+XO-induced inhibition of platelet-mediated relaxation, but it abolished the X+XO-induced contraction of rings as well as subsequent potentiation of norepinephrine-mediated contraction. Pretreatment of rings with hydroxyl radical scavengers dimethyl-2-thiourea, dimethyl sulfoxide, mannitol, or histidine attenuated the X+XO-induced inhibition of platelet-mediated relaxation, although these agents did not affect X+XO-induced contraction of rings. This study indicates that the vasoconstriction on exposure of aortic rings to X+XO is due to generation of superoxide anions, whereas inhibition of platelet-mediated relaxation after exposure of vessels to X+XO is due, at least in part, to release of hydroxyl radicals. Release of superoxide anions and hydroxyl radicals after temporary arterial occlusion may be the basis of subsequent modulation of vascular tone.

Beneficial actions of superoxide dismutase and catalase in stunned myocardium of dogs

1986 ◽  
Vol 250 (3) ◽  
pp. H372-H377 ◽  
Author(s):  
G. J. Gross ◽  
N. E. Farber ◽  
H. F. Hardman ◽  
D. C. Warltier
Keyword(s):  
Blood Flow ◽  
Superoxide Dismutase ◽  
Free Radicals ◽  
Oxygen Free Radicals ◽  
Ischemia Reperfusion ◽  
Free Radical Scavengers ◽  
Stunned Myocardium ◽  
Regional Myocardial Blood Flow ◽  
Control Group ◽  
Myocardial Segment

Recent evidence suggests that oxygen free radicals may partially mediate irreversible ischemia-reperfusion injury in the myocardium. In the present study, the effect of a combination of two oxygen free radical scavengers, superoxide dismutase plus catalase (SOD + CAT), on the recovery of subendocardial segment function following 15 min of coronary artery occlusion followed by 3 h of reperfusion ("stunned" myocardium) was compared with a control group in barbital-anesthetized dogs. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic areas was measured by sonomicrometry and regional blood flow by radioactive microspheres. SOD and CAT were infused into the left atrium 30 min before and throughout the occlusion period. Compared with the control group, %SS in the subendocardium of the ischemic region was significantly (P less than 0.05) greater in the SOD plus CAT-treated group during occlusion and throughout reperfusion. Since there were no significant differences in hemodynamics or regional myocardial blood flow between the SOD plus CAT and the control groups, these results suggest that toxic oxygen free radicals may be partially involved in the reversible ischemic injury that occurs during short periods of coronary occlusion followed by reperfusion.

Real time endoscopical visualization of oxygen free radicals generation during stomach ischemia-reperfusion

2001 ◽  
Vol 120 (5) ◽  
pp. A218
Author(s):  
Veronica Ojetti ◽  
Cristiana Di Campli ◽  
Maurizio Gabrielli ◽  
Massimo Mutignani ◽  
Giovanni Gasbarrini ◽  
...  
Keyword(s):  
Free Radicals ◽  
Real Time ◽  
Oxygen Free Radicals ◽  
Ischemia Reperfusion

Modification of cardiac adrenergic receptors by oxygen free radicals

1991 ◽  
Vol 260 (3) ◽  
pp. H821-H826 ◽  
Author(s):  
M. Kaneko ◽  
D. C. Chapman ◽  
P. K. Ganguly ◽  
R. E. Beamish ◽  
N. S. Dhalla
Keyword(s):  
Free Radicals ◽  
Xanthine Oxidase ◽  
Binding Sites ◽  
Adrenergic Receptors ◽  
Oxygen Free Radicals ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Alpha Adrenergic Receptors ◽  
Cgp 12177 ◽  
Number Of Binding Sites

To examine the effects of oxygen free radicals on alpha- and beta-adrenergic receptors, rat heart crude membranes were incubated with xanthine plus xanthine oxidase, H2O2, or H2O2 plus Fe2+. The assay of beta-adrenergic receptors involving [3H]dihydroalprenolol (DHA) binding revealed that the maximal number of binding sites (Bmax) and dissociation constant (Kd) were increased by xanthine plus xanthine oxidase. H2O2 increased the Kd value for [3H]DHA binding. When a hydrophilic ligand, [3H]CGP-12177, was used for the beta-adrenergic receptor assay, an increase in Kd value without any changes in Bmax value was evident on treating the membranes with xanthine plus xanthine oxidase. The assay of alpha-adrenergic receptors involving [3H]prazosin binding showed a decrease in the number of binding sites and an increase in Kd value only after a prolonged period of incubation. Both H2O2 and H2O2 plus Fe2+ increased the Kd value for [3H]prazosin without changes in Bmax. Changes in both alpha- and beta-adrenergic receptors similar to those with crude membranes were also seen by employing the purified heart sarcolemmal membranes. These data indicate that adrenergic receptors in the sarcolemmal membranes are modified by oxygen free radicals.

Depression of heart sarcolemmal Ca2+-pump activity by oxygen free radicals

1989 ◽  
Vol 256 (2) ◽  
pp. H368-H374 ◽  
Author(s):  
M. Kaneko ◽  
R. E. Beamish ◽  
N. S. Dhalla
Keyword(s):  
Lipid Peroxidation ◽  
Free Radicals ◽  
Protective Effect ◽  
Oxygen Free Radicals ◽  
Ischemia Reperfusion ◽  
Isolated Rat Heart ◽  
Exact Nature ◽  
Dependent Manner ◽  
Membrane Phospholipids ◽  
Generating System

Although oxygen free radicals have been implicated as mediators of cellular injury in myocardial ischemia-reperfusion, the exact nature of defects produced by these radicals is not clear. Because sarcolemmal Ca2+-pump is involved in the efflux of Ca2+ from the cell, this study was undertaken to examine the effects of oxygen free radicals on sarcolemmal ATP-dependent Ca2+ accumulation and Ca2+-stimulated Mg2+-dependent adenosinetriphosphatase (ATPase) activities as well as lipid peroxidation of membrane phospholipids. Isolated rat heart sarcolemmal membranes were incubated with xanthine + xanthine oxidase [a superoxide anion radical (O2-)-generating system], H2O2, or H2O2 + Fe2+ [a hydroxyl radical (HO.)-generating system] and assayed for Ca2+-pump activities. O2- inhibited the Ca2+-pump activities in a time-dependent manner; a significant inhibition of Ca2+-stimulated ATPase activity was seen after 1 min of incubation. Superoxide dismutase showed a protective effect on depression in Ca2+-pump activities caused by O2-.H2O2 inhibited Ca2+-pump activities in a dose-dependent manner; this inhibition was protected by the addition of catalase. HO. depressed the Ca2+-pump activities to a greater extent in comparison with H2O2. Mannitol showed a protective effect on HO.-induced inhibition of Ca2+-pump activities. The promotion of lipid peroxidation by free radicals was evident from increased formation of malondialdehyde. These results indicate that the sarcolemmal membrane is altered on exposure to oxygen free radicals, and this may result in depressing the Ca2+-pump mechanism for Ca2+ efflux from the myocardial cell.

Effect of Oxygen Free Radicals on Cardiac Contractile Activity and Sarcolemmal Na+–Ca2+ Exchange

1996 ◽  
Vol 1 (3) ◽  
pp. 211-217
Author(s):  
Taku Matsubara ◽  
Naranjan S. Dhalla
Keyword(s):  
Superoxide Dismutase ◽  
Free Radicals ◽  
Xanthine Oxidase ◽  
Cardiac Dysfunction ◽  
Oxygen Free Radicals ◽  
Contractile Activity ◽  
Contractile Force ◽  
Cardiac Contractile ◽  
Intracellular Ca ◽  
Exchange Activity

Background Although oxygen free radicals have been shown to induce myocardial cell damage and cardiac dysfunction, the exact mechanism by which these radicals affect the heart function is not clear. Since the occurrence of intracellular Ca2+ overload is critical in the genesis of cellular damage and cardiac dysfunction, and since the sarcolemmal Na+–Ca2+ exchange is intimately involved in Ca2+ movements in myocardium, this study was undertaken to examine the effects of oxygen free radicals on the relationship between changes in cardiac contractile force development and sarcolemmal Na+–Ca2+ exchange activity. Methods and Results Isolated rat hearts were perfused with a medium containing xanthine plus xanthine oxidase for different times, and changes in contractile force as well as sarcolemmal Na+–Ca2+ exchange activity were monitored. Perfusion of the heart with xanthine plus xanthine oxidase resulted in a transient increase followed by a marked decrease in contractile activity; the resting tension was markedly increased. The xanthine plus xanthine oxidase-induced depression in developed tension, rate of contraction, and rate of relaxation, except the transient increase in contractile activity, was prevented by the addition of catalase, but not by superoxide dismutase, in the perfusion medium. A time-dependent depression in sarcolemmal Na+–Ca2+ was also evident upon perfusing the heart with xanthine plus xanthine oxidase. This depression in Na+-dependent Ca2+ uptake was associated with a decrease in the maximal velocity of reaction without any changes in the affinity of Na+–Ca2+ exchanger for Ca2+. The presence of catalase, unlike superoxide dismutase, prevented the decrease in sarcolemmal Na+–Ca2+ exchange activity in hearts perfused with xanthine plus xanthine oxidase. Conclusion The results support the view that a depression in the sarcolemmal Na+–Ca2+ exchange activity may contribute to the occurrence of intracellular Ca2+ overload and subsequent decrease in contractile activity. Furthermore, these actions of xanthine plus xanthine oxidase in the whole heart appear to be a consequence of H2O2 production rather than the ‘ generation of superoxide radicals.

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