Effects of a Xanthine Oxidase/Hypoxanthine Free Radical and Reactive Oxygen Species Generating System on Endothelial Function in New Zealand White Rabbit Aortic Rings

Dowell, Fiona J.; Hamilton, Carlene A.; McMurray, John J.; Reid, John L.

doi:10.1097/00005344-199312000-00003

Cited by 47 publications

(17 citation statements)

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“…This selective action was investigated further by generating superoxide anion with HX/XO and pyrogallol. These experiments were complicated by the fact that superoxide aniongenerating systems also give rise to other reactive oxygen species such as hydrogen peroxide (H202), hydroxyl radical and peroxynitrite which can damage the endothelium and thereby impair endothelium-dependent relaxations (Kvietys et al, 1989;Beckman et al, 1990;Todoki et al, 1992;Dowell et al, 1993). We wished to examine specifically the interaction between NO and superoxide anion and, consequently, catalase (3000 u ml-') was included in all experiments in order to remove H202.…”

Section: Discussionmentioning

confidence: 99%

Differential sensitivity of basal and acetylcholine‐stimulated activity of nitric oxide to destruction by superoxide anion in rat aorta

Mian

Martin

1995

British J Pharmacology

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1 In this study we compared the ability of superoxide anion to destroy the relaxant activity of basal and acetylcholine (ACh)-stimulated activity of NO in isolated rings of rat aorta. 2 Superoxide dismutase (SOD, 1-300 u ml-') induced a concentration-dependent relaxation of phenylephrine (PE)-induced tone in endothelium-containing rings which was blocked by NG-nitro-Larginine (L-NOARG, 30 gM), but had no effect on endothelium-denuded rings. It was likely therefore that the relaxant action of SOD resulted from protection of basally produced NO from destruction by superoxide anion, generated either within the tissue or in the oxygenated Krebs solution. 3 In contrast, a concentration of SOD (50 u ml-') which produced almost maximal enhancement of basal NO activity, had no effect on ACh (10 nM-3 gM)-induced relaxation.4 In the presence of catalase (3000 u ml-') to prevent the actions of hydrogen peroxide, superoxide anion generation using hypoxanthine (HX, 0.1 mM)/xanthine oxidase (XO, 16 mu ml-') produced an augmentation of PE-induced tone in endothelium-containing but not endothelium-denuded rings. This was likely to have resulted from removal of the tonic vasodilator action of basally-produced NO by superoxide anion, since it was blocked in tissues treated with SOD (250 u ml-'), N0-monomethyl-Larginine (L-NMMA, 30 gM) or L-NOARG (30 gM). Pyrogallol (0.1 mM) had a similar action to HX/XO, but produced an additional augmentation of tone by an endothelium-independent mechanism. 5 In contrast to their ability to destroy almost completely the basal activity of NO, HX (0.1 mM)/XO (16 mu ml-') and pyrogallol (0.1 mM) had no effect on ACh-induced relaxation at any concentration. An increase in the concentration of HX to 1 mM or pyrogallol to 0.3 mM did, however, lead to a profound decrease in the magnitude and time course of ACh-induced relaxation at all concentrations. 6 Treatment with diethyldithiocarbamate (DETCA, 0.1 mM, 1 h) to inhibit endogenous Cu-Zn SOD, augmented PE-induced tone in endothelium-containing rings and abolished the ability of HX (0.1 mM)/ XO (16 mu ml-') and L-NMMA (30 gM) to augment tone. It was likely that DETCA had led to the destruction of basal NO activity by increasing superoxide anion levels since its actions were reversed by exogenous SOD (10-300 u ml-'). 7 In contrast to its ability to destroy basal activity of NO completely, DETCA (0.1 mM) produced only a slight blockade of ACh-induced relaxation. However, if these tissues were subsequently treated with concentrations of HX (0.1 mM)/XO (16 mu ml-') or pyrogallol (0.1 mM), which had no effect by themselves on ACh-induced relaxation, a profound blockade was seen and this was reversed completely with SOD (250 u ml-'). 8 The data suggest that basal activity of NO is more sensitive to inactivation by superoxide anion than ACh-stimulated activity and this probably results from differential protection by endogenous Cu-Zn SOD. It is possible therefore that endogenous SOD lowers superoxide anion levels to such an extent that only small amounts of ...

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Section: Discussionmentioning

confidence: 99%

Differential sensitivity of basal and acetylcholine‐stimulated activity of nitric oxide to destruction by superoxide anion in rat aorta

Mian

Martin

1995

British J Pharmacology

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“…1 Substances that generate superoxide (such as pyrogallol, tetrahydrobiopterin, amyloid ␤ peptide, and xanthine/xanthine oxidase) impair endothelium-dependent relaxation of blood vessels. 5,6,8,9 Under these conditions, impairment of endothelium-dependent relaxation is most likely due to interaction of superoxide with nitric oxide and reduction in nitric oxide bioavailability, because superoxide scavengers are effective in protecting vascular function. 5,6,8,9 Thus, local vascular levels of superoxide appear to have profound effects on endothelium-dependent relaxation.…”

mentioning

confidence: 99%

Increased Superoxide and Vascular Dysfunction in CuZnSOD-Deficient Mice

Didion

Ryan

Didion

et al. 2002

Circulation Research

211

189

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Abstract-Increased superoxide is thought to play a major role in vascular dysfunction in a variety of disease states.Superoxide dismutase (SOD) limits increases in superoxide; however, the functional significance of selected isoforms of SOD within the vessel wall are unknown. We tested the hypothesis that selective loss of CuZnSOD results in increased superoxide and altered vascular responsiveness in CuZnSOD-deficient (CuZnSOD Ϫ/Ϫ ) mice compared with wild-type (CuZnSOD ϩ/ϩ ) littermates. Total SOD activity was reduced (PϽ0.05) by approximately 60% and CuZnSOD protein was absent in aorta from CuZnSOD Ϫ/Ϫ as compared with wild-type mice. Vascular superoxide levels, measured using lucigenin (5 mol/L)-enhanced chemiluminescence and hydroethidine (2 mol/L)-based confocal microscopy, were increased (approximately 2-fold; PϽ0.05) in CuZnSOD Ϫ/Ϫ mice as compared with wild-type mice. Relaxation of the carotid artery in response to acetylcholine and authentic nitric oxide was impaired (PϽ0.05) in CuZnSOD Ϫ/Ϫ mice. For example, maximal relaxation to acetylcholine (100 mol/L) was 50Ϯ6% and 69Ϯ5% in CuZnSOD Ϫ/Ϫ and wild-type mice, respectively. Contractile responses of the carotid artery were enhanced (PϽ0.05) in CuZnSOD Ϫ/Ϫ mice in response to phenylephrine and serotonin, but not to potassium chloride or U46619. In vivo, dilatation of cerebral arterioles (baseline diameterϭ31Ϯ1 m) to acetylcholine was reduced by approximately 50% in CuZnSOD Ϫ/Ϫ mice as compared with wild-type mice (PϽ0.05). These findings provide the first direct insight into the functional importance of CuZnSOD in blood vessels and indicate that this specific isoform of SOD limits increases in superoxide under basal conditions. CuZnSOD-deficiency results in altered responsiveness in both large arteries and microvessels.

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“…When xanthine oxidase converts Hyp to xanthine in the presence of molecular oxygen, superoxide radical is generated. SOD, CAT, GSH, and GPx are involved in defense against these processes (Dowell et al, 1993). In the present study we evaluated the correlation between the concentration of ischemia markers (Hyp or Ino) and the activity of erythrocyte SOD, CAT, as well as GPx.…”

Section: Hypoxanthine As a Graft Ischemia Marker And Catalase Activitmentioning

confidence: 99%

“…When xanthine oxidase converts hypoxanthine to xanthine in the presence of molecular oxygen, superoxide radicals are released. Reactive oxygen species generated during ischemia-reperfusion play a major role in microvascular dysfunction and exert direct tissue damage, leading to lipid peroxidation, denaturation of proteins, and oxidation of DNA (Dowell et al, 1993). During ischemia, elevated concentrations of inosine, hypoxanthine and xanthine may occur due to the breakdown of ATP (Kurokawa et al, 1996).…”

Section: Oxypurine and Purine Nucleoside Concentrations In Renal Veinmentioning

confidence: 99%

“…The catabolism of adenine nucleotides results in an accumulation of Hyp in ischemic cells. Also, ischemia is associated with the proteolytic conversion of xanthine dehydrogenase to xanthine oxidase (Dowell et al, 1993). When xanthine oxidase converts Hyp to Xan in the presence of molecular oxygen, superoxide radical is generated.…”

Section: Oxypurine and Nucleoside Concentrations In Renal Veins Durinmentioning

confidence: 99%

See 1 more Smart Citation

Ischemia-Reperfusion Injury in the Transplanted Kidney Based on Purine Metabolism Markers and Activity of the Antioxidant System

Domański¹,

Kłoda²,

Ciechanowski³

2012

Organ Donation and Transplantation - Public Policy and Clinical Perspectives

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Effects of a Xanthine Oxidase/Hypoxanthine Free Radical and Reactive Oxygen Species Generating System on Endothelial Function in New Zealand White Rabbit Aortic Rings

Cited by 47 publications

References 0 publications

Differential sensitivity of basal and acetylcholine‐stimulated activity of nitric oxide to destruction by superoxide anion in rat aorta

Differential sensitivity of basal and acetylcholine‐stimulated activity of nitric oxide to destruction by superoxide anion in rat aorta

Increased Superoxide and Vascular Dysfunction in CuZnSOD-Deficient Mice

Ischemia-Reperfusion Injury in the Transplanted Kidney Based on Purine Metabolism Markers and Activity of the Antioxidant System

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