Chronic exposure to nicotine alters endothelium-dependent arteriolar dilatation: effect of superoxide dismutase

1999 ◽  
Vol 86 (4) ◽  
pp. 1126-1134 ◽  
Author(s):  
William G. Mayhan ◽  
Glenda M. Sharpe
Keyword(s):  
Superoxide Dismutase ◽  
Free Radicals ◽  
Chronic Exposure ◽  
Chronic Treatment ◽  
Cheek Pouch ◽  
Oxygen Derived Free Radicals ◽  
Similar Dose ◽  
Chronic Injection ◽  
Selective Impairment

The first goal of this study was to determine whether chronic injection of nicotine alters endothelium-dependent arteriolar dilatation. We measured the diameter of cheek pouch resistance arterioles (∼50 μm in diameter) in response to endothelium-dependent (acetylcholine and ADP) and -independent (nitroglycerin) agonists in control hamsters and hamsters treated with nicotine (2 μg ⋅ kg−1 ⋅ day−1for 2–3 wk). In control hamsters, acetylcholine (0.1 and 1.0 μM) dilated arterioles by 13 ± 2 and 31 ± 3%, respectively, and ADP (1.0 and 10 μM) dilated arterioles by 18 ± 1 and 30 ± 1%, respectively. In contrast, acetylcholine (0.1 and 1.0 μM) dilated arterioles by only 5 ± 2 and 12 ± 3%, respectively, and ADP (1.0 and 10 μM) dilated arterioles by only 7 ± 2 and 13 ± 3%, respectively, in animals treated with nicotine ( P < 0.05 vs. response in control hamsters). Nitroglycerin produced similar dose-related dilatation of cheek pouch arterioles in control and nicotine-treated hamsters. Our second goal was to examine a possible mechanism for impaired endothelium-dependent arteriolar dilatation during chronic treatment with nicotine. We found that superfusion of the cheek pouch microcirculation with superoxide dismutase (150 U/ml) restored impaired endothelium-dependent, but did not alter endothelium-independent, arteriolar dilatation in hamsters treated with nicotine. Superfusion with superoxide dismutase did not alter endothelium-dependent or -independent arteriolar dilatation in control hamsters. We suggest that chronic exposure to nicotine produces selective impairment of endothelium-dependent arteriolar dilatation via a mechanism related to the synthesis/release of oxygen-derived free radicals.

Superoxide dismutase restores endothelium-dependent arteriolar dilatation during acute infusion of nicotine

1998 ◽  
Vol 85 (4) ◽  
pp. 1292-1298 ◽  
Author(s):  
William G. Mayhan ◽  
Glenda M. Sharpe
Keyword(s):  
Superoxide Dismutase ◽  
Free Radicals ◽  
Topical Application ◽  
Oxygen Radicals ◽  
Cheek Pouch ◽  
Oxygen Derived Free Radicals ◽  
Before And After

We previously showed [ Am. J. Physiol. 272 ( Heart Circ. Physiol. 41): H2337–H2342, 1997] that nicotine impairs endothelium-dependent arteriolar dilatation. However, mechanisms that accounted for the effect of nicotine on endothelium-dependent vasodilatation were not examined. Thus the goal of this study was to examine the role of oxygen radicals in nicotine-induced impairment of arteriolar reactivity. We measured diameter of cheek pouch resistance arterioles (∼50 μm diameter) in response to endothelium-dependent (ACh and ADP) and -independent (nitroglycerin) agonists before and after infusion of vehicle or nicotine in the absence or presence of superoxide dismutase. ACh, ADP, and nitroglycerin produced dose-related dilatation of cheek pouch arterioles before infusion of vehicle or nicotine. Infusion of vehicle, in the absence or presence of superoxide dismutase (150 U/ml), did not alter endothelium-dependent or -independent arteriolar dilatation. In contrast, infusion of nicotine (2 μg ⋅ kg−1 ⋅ min−1) impaired endothelium-dependent, but not -independent, arteriolar dilatation. In addition, the effect of nicotine on endothelium-dependent vasodilatation was reversed by topical application of superoxide dismutase. We suggest that nicotine impairs endothelium-dependent arteriolar dilatation via an increase in the synthesis/release of oxygen-derived free radicals.

Oxidative Stress in Critically Ill Patients

2002 ◽  
Vol 11 (6) ◽  
pp. 543-551 ◽  
Author(s):  
Caryl Goodyear-Bruch ◽  
Janet D. Pierce
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Free Radicals ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Oxygen Free Radicals ◽  
Oxygen Species ◽  
Defense System ◽  
Oxygen Derived Free Radicals

Oxygen-derived free radicals play an important role in the development of disease in critically ill patients. Normally, oxygen free radicals are neutralized by antioxidants such as vitamin E or enzymes such as superoxide dismutase. However, in patients who require intensive care, oxygen free radicals become a problem when either a decrease in the removal or an overproduction of the radicals occurs. This oxidative stress and the damage due to it have been implicated in many diseases in critically ill patients. Many drugs and treatments now being investigated are directed toward preventing the damage from oxidative stress. The formation of reactive oxygen species, the damage caused by them, and the body’s defense system against them are reviewed. New interventions are described that may be used in critically ill patients to prevent or treat oxidative damage.

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.

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.

Superoxide dismutase enhances recovery following myocardial ischemia

1985 ◽  
Vol 248 (5) ◽  
pp. H637-H643 ◽  
Author(s):  
K. P. Burton
Keyword(s):  
Superoxide Dismutase ◽  
Free Radicals ◽  
Myocardial Damage ◽  
Normal Structure ◽  
Severe Damage ◽  
Resting Tension ◽  
Oxygen Derived Free Radicals ◽  
Perfusion Solution ◽  
Vessel Structure ◽  
Contractile Performance

Oxygen-derived free radicals, specifically superoxide (O-2) and the hydroxyl radical (OH.), have been implicated as possible mediators in the development of myocardial damage induced by ischemia and reflow. The purpose of this study was to examine the ability of superoxide dismutase (SOD), a O-2 scavenging enzyme, to protect the heart against functional and structural alterations due to ischemia and reflow. An isolated perfused rabbit interventricular septal preparation was used for these experiments. Septa were treated with SOD by adding either 10 or 20 micrograms/ml of the enzyme to the perfusion solution 15 min prior to ischemia and during reflow. Other septa were not treated. Septa were made ischemic for 1 h and reperfused for 1 h. The contractile performance of reperfused septa was found to be significantly improved in SOD-treated septa when compared with nontreated septa. After 60 min of reflow, values for nontreated, 10- and 20-micrograms/ml SOD-treated septa, respectively, were 48.5 +/- 5.2 (SE), 67.4 +/- 4.2, and 82.0 +/- 3.8% of control values for developed tension. The rise in resting tension observed with reflow was significantly decreased. SOD treatment also provided significant protection of myocardial ultrastructure. The percent of myocytes showing normal structure was increased approximately 40%, and the percentages of myocytes showing mild or severe damage were decreased approximately 30 and 15%, respectively, for SOD-treated septa. Vessel structure showed a similar trend. Thus SOD preserves myocardial function and structure in septa reperfused following ischemia. These results support the possibility that oxygen-derived free radicals may be involved in the damage resulting from ischemia and reflow.

scholarly journals Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor

1986 ◽  
Vol 250 (5) ◽  
pp. H822-H827 ◽  
Author(s):  
G. M. Rubanyi ◽  
P. M. Vanhoutte
Keyword(s):  
Endothelial Cells ◽  
Superoxide Dismutase ◽  
Biological Activity ◽  
Free Radicals ◽  
Protective Effect ◽  
Femoral Artery ◽  
Superoxide Anions ◽  
Relaxing Factor ◽  
Oxygen Derived Free Radicals ◽  
Endothelium Derived Relaxing Factor

Experiments were designed to determine the effects of oxygen-derived free radicals on the production and biological activity of endothelium-derived relaxing factor or factors released by acetylcholine. Rings of canine coronary arteries without endothelium (bioassay rings) were superfused with solution passing through a canine femoral artery with endothelium. Superoxide dismutase caused maximal relaxation of the bioassay ring when infused upstream, but not downstream, of the femoral artery; this effect of superoxide dismutase was inhibited by catalase. Infusion of acetylcholine relaxed the bioassay rings because it released a labile relaxing factor (or factors) from the endothelium. When infused below the femoral artery, superoxide dismutase and, to a lesser extent, catalase augmented the relaxations to acetylcholine. Superoxide dismutase, but not catalase, doubled the half-life of the endothelium-derived relaxing factor(s). This protective effect of the enzyme was augmented fivefold by lowering the oxygen content of the perfusate from 95 to 10%. These data demonstrate that: superoxide anions inactivate the relaxing factor(s) released by acetylcholine from endothelial cells and hyperoxia favors the inactivation of endothelium-derived relaxing factor(s).

Sign in / Sign up

Export Citation Format

Share Document