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.

Nicotine impairs histamine-induced increases in macromolecular efflux: role of oxygen radicals

1998 ◽  
Vol 84 (5) ◽  
pp. 1589-1595 ◽  
Author(s):  
William G. Mayhan ◽  
Glenda M. Sharpe
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Smokeless Tobacco ◽  
Oxygen Radicals ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Macromolecular Transport ◽  
Before And After ◽  
Oxide Synthase

Nicotine, a major component of cigarettes and smokeless tobacco, has toxic effects on endothelium and impairs reactivity of resistance arterioles in response to agonists that stimulate the synthesis and/or release of nitric oxide. However, the effect of nicotine on nitric oxide synthase-dependent increases in macromolecular transport is not known. Thus our first goal was to determine the effect of nicotine on histamine-induced increases in macromolecular efflux. We used intravital microscopy and FITC dextran (mol wt 70,000) (FITC-dextran-70K) to examine macromolecular extravasation from postcapillary venules in response to histamine before and after intravenous infusion of vehicle or nicotine. Extravasation of macromolecules was quantitated by counting venular leaky sites and calculating clearance (ml/s × 10−6) of FITC-dextran-70K. Histamine elicited reproducible increases in venular leaky sites and clearance in hamsters infused with vehicle. In contrast, nicotine infusion inhibited histamine-induced increases in macromolecular efflux. Histamine (1.0 and 5.0 μM) elicited 19 ± 2 and 34 ± 4 vs. 3 ± 1 and 11 ± 5 leaky sites per 0.11 cm2, before vs. after nicotine infusion, respectively ( P < 0.05). Histamine-induced clearance of FITC-dextran-70K was also impaired after infusion of nicotine. Our second goal was to examine whether alterations in histamine-induced increases in macromolecular efflux by nicotine may be related to the production of oxygen radicals. Application of superoxide dismutase (150 U/ml) to the hamster cheek pouch restored histamine-induced increases in venular leaky sites and clearance of FITC-dextran-70K during infusion of nicotine. Thus nicotine alters agonist-induced increases in microvascular permeability, via the formation of oxygen radicals, to presumably inactivate nitric oxide.

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.

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.

The Role of Oxygen-Derived Free Radicals and Nitric Oxide in Cytokine-Induced Antiproliferation of Pancreatic Cancer Cells

Pancreas ◽  
2002 ◽  
Vol 24 (2) ◽  
pp. 161-168 ◽  
Author(s):  
William J. Thomas ◽  
Deborah L. Thomas ◽  
Joseph A. Knezetic ◽  
Thomas E. Adrian
Keyword(s):  
Nitric Oxide ◽  
Pancreatic Cancer ◽  
Free Radicals ◽  
Cancer Cells ◽  
Pancreatic Cancer Cells ◽  
Oxygen Derived Free Radicals

Temporal effect of alcohol consumption on reactivity of pial arterioles: role of oxygen radicals

2001 ◽  
Vol 280 (3) ◽  
pp. H992-H1001 ◽  
Author(s):  
Hong Sun ◽  
William G. Mayhan
Keyword(s):  
Nitric Oxide ◽  
Free Radicals ◽  
Alcohol Consumption ◽  
Nitric Oxide Synthase ◽  
Chronic Alcohol ◽  
Chronic Alcohol Consumption ◽  
Oxygen Derived Free Radicals ◽  
Pial Arterioles ◽  
Oxide Synthase

Chronic alcohol consumption reduces nitric oxide synthase-dependent responses of pial arterioles via mechanisms that remain uncertain. In addition, the temporal effects of alcohol on pial arterioles is unclear. Thus our goals were to examine the role of oxygen-derived free radicals in alcohol-induced impairment of cerebrovascular reactivity and the temporal effect of alcohol on reactivity of pial arterioles. Sprague-Dawley rats were pair-fed a liquid diet with or without alcohol for 2–3 wk, 2–3 mo, or 5–6 mo. We measured the in vivo diameter of pial arterioles in response to nitric oxide synthase-dependent dilators acetylcholine and ADP and the nitric oxide synthase-independent dilator nitroglycerin. In nonalcohol-fed rats, acetylcholine (1.0 and 10 μM) and ADP (10 and 100 μM) produced dose-related dilatation of pial arterioles. Whereas there was no difference in reactivity of arterioles to the agonists in rats fed the nonalcohol and alcohol diets for a period of 2–3 wk, there was a significant impairment in reactivity of arterioles to acetylcholine and ADP, but not nitroglycerin, in rats fed the alcohol diet for longer durations. We then found that treatment with superoxide dismutase did not alter baseline diameter of pial arterioles in nonalcohol-fed or alcohol-fed rats, but significantly improved impaired nitric oxide synthase-dependent dilatation of pial arterioles in alcohol-fed rats. Thus our findings suggest a temporal relationship in the effects of alcohol on reactivity of pial arterioles and that impaired nitric oxide synthase-dependent cerebral vasodilatation during chronic alcohol consumption may be related, in part, to enhanced release of oxygen-derived free radicals.

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