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

1993 ◽  
Vol 264 (3) ◽  
pp. H859-H864 ◽  
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.

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

1986 ◽  
Vol 250 (5) ◽  
pp. H815-H821 ◽  
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.

Endothelial L-arginine pathway and relaxations to vasopressin in canine basilar artery

1993 ◽  
Vol 264 (2) ◽  
pp. H413-H418 ◽  
Author(s):  
F. Cosentino ◽  
J. C. Sill ◽  
Z. S. Katusic
Keyword(s):  
Nitric Oxide ◽  
Basilar Artery ◽  
Isometric Tension ◽  
Nitric Oxide Donor ◽  
Basal Tone ◽  
Basilar Arteries ◽  
Canine Basilar Artery ◽  
Subsequent Activation ◽  
Oxide Synthase

Experiments were designed to determine the role of the L-arginine pathway in endothelium-dependent relaxations to vasopressin. The effects of L-arginine analogues NG-nitro-L-arginine (L-NNA), NG-nitro-L-arginine methyl ester (L-NAME), and NG-monomethyl-L-arginine (L-NMMA) on basal and vasopressin-induced activity of nitric oxide synthase were studied in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (37 degrees C, pH 7.4). Radioimmunoassay was used to determine the level of guanosine 3',5'-cyclic monophosphate (cGMP). All experiments were performed in the presence of indomethacin, a cyclooxygenase inhibitor. L-NAME and L-NMMA caused endothelium-dependent contractions and inhibited basal production of cGMP. In contrast, L-NNA did not affect basal tone or basal production of cGMP. L-Arginine analogues inhibited relaxations to vasopressin but did not affect relaxations to a nitric oxide donor, molsidomine (SIN-1). The effects of L-NNA, L-NAME, and L-NMMA were reversed in the presence of L-arginine. The relaxations to vasopressin were associated with an increase of cGMP levels in the arterial wall. This effect of vasopressin was inhibited in the presence of L-NNA. These studies suggest that the relaxations to vasopressin are mediated by activation of the endothelial L-arginine pathway, leading to increased production of nitric oxide, with subsequent activation of guanylate cyclase in smooth muscle cells. In canine basilar artery, L-NAME and L-NMMA are nonselective inhibitors of both basal and stimulated production of nitric oxide, whereas L-NNA selectively inhibits vasopressin-induced activation of the L-arginine pathway.

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

2015 ◽  
pp. 149-164 ◽  
Author(s):  
David J. Hearse ◽  
Allan S. Manning ◽  
James M. Downey ◽  
Derek M. Yellon
Keyword(s):  
Free Radicals ◽  
Xanthine Oxidase ◽  
Myocardial Injury ◽  
Critical Role ◽  
Oxygen Derived Free Radicals

Relaxation of canine coronary artery to electrical stimulation: limited role of free radicals

1987 ◽  
Vol 253 (4) ◽  
pp. H884-H889
Author(s):  
M. Feletou ◽  
P. M. Vanhoutte
Keyword(s):  
Superoxide Dismutase ◽  
Electrical Stimulation ◽  
Free Radicals ◽  
Coronary Artery ◽  
Isometric Tension ◽  
Chloride Ions ◽  
Sodium Ascorbate ◽  
Second Phase ◽  
Oxygen Derived Free Radicals ◽  
Canine Coronary Artery

Electrical stimulation induces tetrodotoxin-insensitive relaxation of the canine coronary artery. The present study was designed to verify whether this relaxation involves the production of oxygen-derived free radicals. Isolated rings of canine coronary arteries were suspended for isometric tension recording in organ chambers filled with Krebs-Ringer bicarbonate solution. They were stimulated electrically (9 V, 3 Hz, 2 ms for 2 min) by means of two platinum electrodes during contractions evoked by various vasoactive agonists. Under control conditions, electrical stimulation caused rapid, reversible relaxations. Superoxide dismutase in association with catalase or mannitol, sodium ascorbate, dimethyl sulfoxide, and glutathione did not inhibit the relaxation caused by stimulation applied for only 2 min; neither did the removal of chloride ions from the salt solution nor the association of Cl-free solution in the presence of mannitol, superoxide dismutase, and catalase. Prolonging the electrical stimulation (9 V, 3 Hz, 2 ms) for up to 20 min produced a secondary relaxation. This second phase was inhibited by sodium ascorbate. These experiments indicate that the rapid relaxation induced by short-lasting electrical stimulation is probably not due to the generation of oxygen-derived free radicals. However, prolonged stimulation causes the production of such radicals, which then evoke irreversible inhibition of the vascular smooth muscle of the canine coronary artery.

Effects of prolonged exposure to oxygen-derived free radicals in canine pulmonary arteries

1996 ◽  
Vol 270 (6) ◽  
pp. H2184-H2190 ◽  
Author(s):  
L. Wiklund ◽  
C. G. McGregor ◽  
V. M. Miller
Keyword(s):  
Superoxide Dismutase ◽  
Free Radicals ◽  
Xanthine Oxidase ◽  
Vascular Injury ◽  
Prolonged Exposure ◽  
Isometric Force ◽  
Pulmonary Arteries ◽  
Calcium Ionophore ◽  
Oxygen Derived Free Radicals ◽  
A 23187

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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