Effects of vitamin C and of a cell permeable superoxide dismutase mimetic on acute lipoprotein induced endothelial dysfunction in rabbit aortic rings

Fontana, Luigi; McNeill, Karen; Ritter, James M.; Chowienczyk, Phil

doi:10.1038/sj.bjp.0702331

Cited by 35 publications

(27 citation statements)

References 36 publications

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“…In the present study, preincubation with Larginine (1 mM) did not a ect the response to Ach, however, indicating that lack of substrate was not a primary cause of endothelial dysfunction. This is in accordance with the failure of L-arginine to improve endothelial function following exposure to LDL in rabbit aortic rings (Fontana et al, 1999). Administration of BH 4 , at a concentration which has been demonstrated to enhance production of NO and restore endothelial function (Cosentino & Katusic 1995;Tiefenbacher et al, 1996;Pieper, 1997), resulted in a slight enhancement but not normalization of endothelial function.…”

Section: Discussionsupporting

confidence: 81%

Endothelial dysfunction in atherosclerotic mice: improved relaxation by combined supplementation with L‐arginine‐tetrahydrobiopterin and enhanced vasoconstriction by endothelin

Jiang

Valen²,

Tokuno³

et al. 2000

British J Pharmacology

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1 Mice lacking the apolipoprotein E and low density lipoprotein receptor genes (E8xLDLR8) develop atherosclerosis and endothelial dysfunction. The aim of this study was to characterize the roles of L-arginine and tetrahydrobiopterin (BH 4 ) for endothelium-dependent relaxation and the changes in the vasoconstrictor response to endothelin-1 (ET-1) in thoracic aortic rings of E8xLDLR8 mice. 2 Histological examination revealed severe atherosclerosis of the thoracic aorta of E8xLDLR8 mice. Relaxations induced by acetylcholine (Ach), but not that to sodium nitroprusside, were signi®cantly impaired in E8xLDLR8 mice compared to control mice indicating attenuated endothelium-dependent relaxations. 3 Preincubation with the nitric oxide (NO) substrate L-arginine did not a ect, whereas the cofactor for NO synthase, BH 4 , slightly improved the relaxations induced by Ach. Combined preincubation with L-arginine and BH 4 induced a pronounced enhancement of Ach-induced relaxations in E8xLDLR8 mice. The relaxations induced by Ach in E8xLDLR8 mice in the presence of L-arginine and BH 4 were not di erent from those observed in control mice. 4 Preincubation with superoxide dismutase did not a ect Ach-induced relaxations in aorta from E8xLDLR8 mice. 5 The contractile response to ET-1 was enhanced in E8xLDLR8 mouse aorta. The contractions were abolished by the ET A receptor antagonist LU 135252. The ET B receptor agonist sarafotoxin 6c did not induce contractions or relaxations. 6 It is concluded that endothelial dysfunction of E8xLDLR8 mouse aorta is reversed by combined administration of L-arginine and BH 4 . In addition, the ET A receptor-mediated vasoconstriction by ET-1 is enhanced in E8xLDLR8 mice.

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Section: Discussionsupporting

confidence: 81%

Endothelial dysfunction in atherosclerotic mice: improved relaxation by combined supplementation with L‐arginine‐tetrahydrobiopterin and enhanced vasoconstriction by endothelin

Jiang

Valen²,

Tokuno³

et al. 2000

British J Pharmacology

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“…A number of SOD mimetics are available that cross the membrane and decrease oxidative stress with improvement of endothelial function [117,118].…”

Section: Mimetics and Stimulators Of Anti-oxidative Enzymesmentioning

confidence: 99%

Oxidative Stress in Cardiovascular Disease: A New Avenue Toward Future Therapeutic Approaches

Inagi

2006

PRC

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Oxidative stress is a common denominator in many aspects of the pathogenesis of atherosclerosis and cardiovascular diseases. Some drugs, such as vitamin C, vitamin E, and a free radical scavenger, edaravone, are prescribed with oxidative stress as their main target. Furthermore, of the drugs in current clinical use, such as anti-hypertension reagents including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB), and anti-hyperlipidemic reagents like statins, protect various organs, e.g., vessel, brain, heart, and kidney, via anti-oxidative stress effects in addition to their original pharmacological properties. While results of clinical trials of anti-oxidative stress reagents in patients with cardiovascular disease are contradictory to date, this may be explained by a variety of reasons such as an inadequate study design. More competent anti-oxidative reagents are awaited, and superoxide dismutase mimetics, thiols, xanthine oxidase and NAD(P)H oxidase inhibitors, which regulate intracellular redox reaction and subsequently inhibit oxidative stress, are among promising candidates of future drug developments currently receiving much interest. In this review, the current advances will be highlighted in development of novel anti-oxidative therapeutic approaches against cardiovascular diseases.

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“…This may be because Cu/Zn SOD does not gain access to the appropriate cellular compartments. However, a number of SOD mimetics are available that cross the membrane and have proved more successful in decreasing oxidative stress and improving endothelial function [15,173].…”

Section: Sod Mimeticsmentioning

confidence: 99%

Strategies to reduce oxidative stress in cardiovascular disease

et al. 2004

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A multitude of studies in experimental animals, together with clinical data, provide evidence that increased production of ROS (reactive oxygen species) are involved in the development and progression of cardiovascular disease. As ROS appear to have a critical role in atherosclerosis, there has been considerable interest in identifying the enzyme systems involved and in developing strategies to reduce oxidative stress. Prospective clinical trials with vitamins and hormone replacement therapy have not fulfilled earlier promises, although there is still interest in other dietary supplements. Superoxide dismutase mimetics, thiols, xanthine oxidase and NAD(P)H oxidase inhibitors are currently receiving much interest, while animal studies using gene therapy show promise, but are still at an early stage. Of the drugs in common clinical use, there is evidence that ACE (angiotensin-converting enzyme) inhibitors and AT1 (angiotensin II type 1) receptor blockers have beneficial effects on oxidative stress above their antihypertensive properties, whereas statins, in addition to improving lipid profiles, may also lower oxidative stress.

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Effects of vitamin C and of a cell permeable superoxide dismutase mimetic on acute lipoprotein induced endothelial dysfunction in rabbit aortic rings

Cited by 35 publications

References 36 publications

Endothelial dysfunction in atherosclerotic mice: improved relaxation by combined supplementation with L‐arginine‐tetrahydrobiopterin and enhanced vasoconstriction by endothelin

Endothelial dysfunction in atherosclerotic mice: improved relaxation by combined supplementation with L‐arginine‐tetrahydrobiopterin and enhanced vasoconstriction by endothelin

Oxidative Stress in Cardiovascular Disease: A New Avenue Toward Future Therapeutic Approaches

Strategies to reduce oxidative stress in cardiovascular disease

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