Oxygen-Derived Free Radicals and Myocardial Injury: A Critical Role for Xanthine Oxidase?1

Experiments were designed to evaluate endothelium-dependent responses of pulmonary arteries following prolonged exposure to oxygen-derived free radicals. Rings of canine pulmonary arteries with and without endothelium were suspended for measurement of isometric force in organ chambers and incubated with xanthine (10(-4)M) plus xanthine oxidase (0.015 U/ml) for 1 h in the absence and presence of either superoxide dismutase (SOD, 150 U/ml), catalase (1,200 U/ml), deferoxamine (10(-3)M), or a combination of all three scavengers. Xanthine plus xanthine oxidase caused significantly greater contractions of rings without compared with those with endothelium. In rings with endothelium, contractions were reduced by SOD or catalase but not by deferoxamine. Following 1 h of exposure to xanthine plus xanthine oxidase, endothelium-dependent relaxations to ADP were reduced but not those to bradykinin or the calcium ionophore A-23187 (calcimycin). Relaxations to ADP were not corrected by incubation with the antioxidants used singly or in combination during the exposure to xanthine plus xanthine oxidase. These results suggest that oxygen-derived free radicals generated from exogenously applied xanthine plus xanthine oxidase cause contractions of canine pulmonary arteries. In addition, even when contractions of rings with endothelium were prevented by SOD and catalase, subsequent expression of some but not all endothelium-dependent relaxations were reduced. Therefore, scavenging of oxygen-derived free radicals may prevent some but not all of the vascular injury caused by oxygen-derived free radicals.

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Histamine, xanthine oxidase generated oxygen-derived free radicals and Helicobacter pylori in gastroduodenal inflammation and ulceration

Inflammation Research ◽

10.1007/s000110050317 ◽

1998 ◽

Vol 47 (4) ◽

pp. 193-199 ◽

Cited By ~ 8

Author(s):

A. Ben-Hamida ◽

W. K. Man ◽

N. McNeil ◽

J. Spencer

Keyword(s):

Helicobacter Pylori ◽

Free Radicals ◽

Xanthine Oxidase ◽

Oxygen Derived Free Radicals

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Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1986.250.5.h815 ◽

1986 ◽

Vol 250 (5) ◽

pp. H815-H821 ◽

Cited By ~ 30

Author(s):

G. M. Rubanyi ◽

P. M. Vanhoutte

Keyword(s):

Hydrogen Peroxide ◽

Superoxide Dismutase ◽

Smooth Muscle ◽

Free Radicals ◽

Vascular Smooth Muscle ◽

Xanthine Oxidase ◽

Isometric Tension ◽

Oxygen Derived Free Radicals ◽

Major Shift ◽

The Right

Experiments were designed to determine the role of oxygen-derived free radicals in modulating contractions of vascular smooth muscle and endothelium-mediated relaxations to acetylcholine. The effects of generating or scavenging these radicals were studied in rings of canine coronary arteries suspended for isometric tension recording. Xanthine oxidase plus xanthine caused relaxations, which were greater in rings with endothelium than in rings without endothelium; the relaxations were not affected by superoxide dismutase or mannitol, but could be prevented by catalase. Xanthine oxidase plus xanthine depressed endothelium-mediated relaxations to acetylcholine; this effect was prevented by superoxide dismutase, but was not affected by catalase or mannitol. Exogenous hydrogen peroxide induced catalase-sensitive relaxations, which were depressed by the removal of the endothelium. Superoxide dismutase evoked catalase-sensitive relaxations only in rings with endothelium. Endothelium-mediated relaxations to acetylcholine were slightly depressed by superoxide dismutase or catalase alone; the combination of the two enzymes or mannitol caused a major shift to the right of the concentration-response curve to acetylcholine. In rings without endothelium, relaxations caused by sodium nitroprusside were not affected by the scavengers (alone or in combination) but were augmented by xanthine oxidase plus xanthine. These data suggest that the endothelium-derived relaxing factor released by acetylcholine is not likely to be an oxygen-derived free radical; hydrogen peroxide has a direct inhibitory action on coronary arterial smooth muscle and triggers endothelium-dependent relaxations; and superoxide anions depress and hydroxyl radicals facilitate endothelium-dependent relaxations caused by activation of muscarinic receptors.

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Oxygen radicals: effects on intestinal vascular permeability

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.247.2.g167 ◽

1984 ◽

Vol 247 (2) ◽

pp. G167-G170 ◽

Cited By ~ 9

Author(s):

D. A. Parks ◽

A. K. Shah ◽

D. N. Granger

Keyword(s):

Free Radicals ◽

Xanthine Oxidase ◽

Vascular Permeability ◽

Oxygen Radicals ◽

Protein Concentration ◽

Intestinal Ischemia ◽

Control Value ◽

Enzyme Substrate ◽

Oxygen Derived Free Radicals ◽

Osmotic Reflection Coefficient

There is now a considerable amount of evidence in the literature implicating oxygen-derived free radicals in the vascular permeability changes associated with intestinal ischemia. To directly assess the effects of oxygen radicals on vascular permeability, hypoxanthine-xanthine oxidase, an enzyme-substrate system known to generate oxygen free radicals, was infused into the arterial supply of autoperfused segments of cat ileum. The osmotic reflection coefficient (sigma d) of intestinal capillaries to total plasma proteins was estimated from the steady-state relationship between lymph-to-plasma total protein concentration ratio and lymph flow. Intra-arterial infusion of hypoxanthine-xanthine oxidase reduced sigma d from a control value of 0.92 to 0.66, indicating an increased vascular permeability. This increase in vascular permeability was significantly attenuated by the addition of superoxide dismutase (sigma d = 0.86), a specific scavenger of superoxide anion (O2-), or dimethylsulfoxide (sigma d = 0.83), the hydroxyl radical (OH X) scavenger, to the infusate. The results of this study indicate that oxygen-derived free radicals, generated by the reaction of hypoxanthine with xanthine oxidase, increase intestinal vascular permeability to an extent comparable with that observed in preparations subjected to 1 h of ischemia.

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Endothelium-dependent contractions to oxygen-derived free radicals in the canine basilar artery

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.264.3.h859 ◽

1993 ◽

Vol 264 (3) ◽

pp. H859-H864 ◽

Cited By ~ 14

Author(s):

Z. S. Katusic ◽

J. Schugel ◽

F. Cosentino ◽

P. M. Vanhoutte

Keyword(s):

Hydrogen Peroxide ◽

Free Radicals ◽

Xanthine Oxidase ◽

Isometric Tension ◽

Thromboxane B2 ◽

Prostaglandin F2 Alpha ◽

Oxygen Derived Free Radicals ◽

Basilar Arteries ◽

Canine Basilar Artery ◽

Effect Of Oxygen

Experiments were designed to determine the effect of oxygen-derived free radicals in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution bubbled with 95% O2-5% CO2 (temperature = 37 degrees C; pH = 7.4). A radioimmunoassay technique was used to measure production of prostaglandins and thromboxane B2. Xanthine oxidase (1-9 mU/ml, in the presence of 10(-4) M xanthine) and hydrogen peroxide (10(-6) to 10(-4) M) caused concentration-dependent contractions. The removal of endothelium reversed these contractions into relaxations. Contractions to xanthine oxidase and hydrogen peroxide were inhibited in the presence of superoxide dismutase (150 U/ml), catalase (1,200 U/ml), indomethacin (10(-5) M), and SQ 29548 (10(-6) M) but not in the presence of deferoxamine (10(-4) to 10(-3) M) and dimethyl sulfoxide (10(-4) M). NG-monomethyl-L-arginine (3 x 10(-5) M) augmented the contractions to hydrogen peroxide. Xanthine oxidase stimulated production of 6-ketoprostaglandin F1 alpha, prostaglandin F2 alpha, prostaglandin E2, and thromboxane B2. The stimulatory effect was prevented by the removal of endothelial cells. These studies suggest that xanthine oxidase causes endothelium-dependent contractions mediated by: 1) hydrogen peroxide-induced stimulation of the endothelial metabolism of arachidonic acid via the cyclooxygenase pathway, leading to activation of prostaglandin H2-thromboxane A2 receptors, and 2) inactivation of basal production of nitric oxide by superoxide anions.

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