Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats.

Lefer, David J.; Scalia, Rosario; Campbell, Barry; Nossuli, Tareck O.; Hayward, Reid; Salamon, Magdalena; Grayson, John W.; Lefer, Allan M.

doi:10.1172/jci119212

Cited by 248 publications

(162 citation statements)

References 52 publications

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“…These findings as well as other studies [25,26], suggest that PN can exert a cytoprotective function, whereas PN oxidative stress worsens pathologic conditions [244][245][246]. Certainly, the imbalance between NO and superoxide has been implicated in inflammatory disease states [57,165,[247][248][249].…”

Section: Anti-platelet Aggregation Effects Of Peroxynitritesupporting

confidence: 64%

“…These data show that PN in a macromolar range can exert significant vasorelaxant effects in isolated vessels. The administration of acetylcholine following the administration of 5 M of PN to the ring preparation produced a significant relaxation suggesting that PN does not impair endothelium dependent responses [26]. The effects of PN were observed on adherence to the endothelium of unstimulated PMNs following thrombin stimulation in isolated superior mesenteric artery.…”

Section: Protective Effect Of Peroxynitrite In Ischemia Reperfusion Imentioning

confidence: 85%

“…Although vascular injury is linked to formation of toxic products from activated neutrophils [104], and that endothelial cells, macrophages and neutrophils can generate PN and induce membrane lipid peroxidation [57], the effects of PN on neutrophilendothelial cell interactions were largely unknown. Lefer, Scalia et al investigated the effect of physiologic relevant concentrations of PN on neutrophil (PMN)-endothelial cell interactions [26]. In rat isolated aorta rings, PN (5 M), but not decomposed PN, produced significant relaxation, whereas at concentrations of 50 nM-500 nM, detectable responses were not seen [26].…”

Section: Protective Effect Of Peroxynitrite In Ischemia Reperfusion Imentioning

confidence: 99%

“…Lefer, Scalia et al investigated the effect of physiologic relevant concentrations of PN on neutrophil (PMN)-endothelial cell interactions [26]. In rat isolated aorta rings, PN (5 M), but not decomposed PN, produced significant relaxation, whereas at concentrations of 50 nM-500 nM, detectable responses were not seen [26]. These data show that PN in a macromolar range can exert significant vasorelaxant effects in isolated vessels.…”

Section: Protective Effect Of Peroxynitrite In Ischemia Reperfusion Imentioning

confidence: 99%

“…In contrast, PN has been shown to have beneficial effects similar to those of NO and has been shown to produce vasorelaxation [20,21], inhibit platelet aggregation [22,23], and can limit ischemia-reproduction injury [24][25][26]. In this review, we describe the progress made in understanding the beneficial role of PN in the cardiovascular system.…”

Section: Introductionmentioning

confidence: 99%

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Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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Peroxynitrite (PN) is generated by the reaction of nitric oxide (NO) and superoxide in one of the most rapid reactions in biology. Studies have reported that PN is a cytotoxic molecule that contributes to vascular injury in a number of disease states. However, it has become apparent that PN has beneficial effects including vasodilation, inhibition of platelet aggregation, inhibition of inflammatory cell adhesion, and protection against ischemia/reperfusion injury in the heart. It is our hypothesis that PN may serve to inactivate superoxide and prolong the actions of NO in the circulation. This manuscript reviews the beneficial effects of PN in the cardiovascular system. Keywords:Nitric oxide/*metabolism, nitric oxide synthase/metabolism/physiology, peroxynitrous acid/metabolism, reactive nitrogen species/metabolism, reactive oxygen species/metabolism, endothelium, vascular/drug effects/metabolism, muscle, smooth, vascular/drug effects/*metabolism, vasodilator agents/adverse effects, oxidative stress/*physiology, vasodilation/drug effects.

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Section: Anti-platelet Aggregation Effects Of Peroxynitritesupporting

confidence: 64%

Section: Protective Effect Of Peroxynitrite In Ischemia Reperfusion Imentioning

confidence: 85%

Section: Protective Effect Of Peroxynitrite In Ischemia Reperfusion Imentioning

confidence: 99%

Section: Protective Effect Of Peroxynitrite In Ischemia Reperfusion Imentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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Nitric Oxide and the Surgical Patient

Tzeng

Billiar²

1997

Arch Surg

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It has been a decade since the elucidation of the key components of L-arginine to the nitric oxide (NO) pathway.1-3 Knowledge in this field has expanded at a dizzying pace such that it is clear that NO participates in some way in essentially every physiologic process. Just as important has been the characterization of roles of NO in the pathophysiological features of many disease processes. New findings appear in the scientific literature at a rate that overwhelms even the most dedicated NO researchers. The universal interest in the biomedical importance of this molecule recently became evident with the creation of the Nitric Oxide Society along with its peer-reviewed publication, Nitric Oxide: Biology and Chemistry. With this tremendous investment of research resources, the clinician cannot help but wonder, "What have we learned that is clinically relevant?" and "Where are the therapeutic dividends?" This article will provide some of the key observations made about NO relevant to the biological responses of surgical patients and discuss some of the therapies based on NO research on the horizon. First, we will summarize basic NO biochemistry. HOW IS NO MADE?Nitric oxide is produced from the amino acid L-arginine via 1 of 3 distinct NO synthases (NOSs) or enzymes (Figure 1 ).4"6 Each isoform differs considerably in its pat¬ tern of expression and regulation. In fact, the amount of NO produced at a specific site is determined primarily by the type of NOS isoform expressed. This is impor¬ tant because the biological consequences of NO are dependent to a considerable de¬ gree on its production rate, and essen¬ tially all of the NO-based therapies repre¬ sent efforts to either remove or supplement NO. Two of the isoforms, NOS-1 and NOS-3, are referred to as constitutive (cNOS) because they are typically ex¬ pressed in cells in the resting state. Nitric oxide synthase-1 was initially identified in neurons and NOS-3 in endothelial cells, hence, the alternative designations neu¬ ronal NOS for type 1 and endothelial NOS (eNOS) for type 3. These isoforms are regulated by calcium fluxes within the cell and produce small amounts of NO tran¬ siently when agonists trigger an eleva¬ tion in intracellular calcium. Agonists dif¬ fer for each cell type, and dysregulated constitutive NOS activity can result from either impaired cell signaling responses re¬ sulting in inadequate NO production or overstimulation resulting in enhanced NO production.In clear distinction from constitu¬ tive NOS, NOS-2, also known as the inducible or inflammatory NOS (iNOS), is active independent of increases in intra¬ cellular calcium and produces NO in a sus¬ tained manner. Although constitutive iNOS expression has been described, in most cell types iNOS expression requires exposure to signals such as cytokines, mi¬ crobes, or microbial products. Thus, one of the most important aspects of the regu¬ lation of iNOS activity is the level of gene expression. Tightly regulated iNOS gene expression is used by the host as an effec¬ tor mechanism during infect...

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Effects of electromagnetic radiation from a cellular telephone on the oxidant and antioxidant levels in rabbits

Irmak

Fadıllıoğlu

Güleç

et al. 2002

Cell Biochemistry & Function

195

108

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The number of reports on the effects induced by electromagnetic radiation (EMR) in various cellular systems is still increasing. Until now no satisfactory mechanism has been proposed to explain the biological effects of this radiation. Oxygen free radicals may play a role in mechanisms of adverse effects of EMR. This study was undertaken to investigate the influence of electromagnetic radiation of a digital GSM mobile telephone (900 MHz) on oxidant and antioxidant levels in rabbits. Adenosine deaminase, xanthine oxidase, catalase, myeloperoxidase, superoxide dismutase (SOD) and glutathione peroxidase activities as well as nitric oxide (NO) and malondialdehyde levels were measured in sera and brains of EMR-exposed and sham-exposed rabbits. Serum SOD activity increased, and serum NO levels decreased in EMR-exposed animals compared to the sham group. Other parameters were not changed in either group. This finding may indicate the possible role of increased oxidative stress in the pathophysiology of adverse effect of EMR. Decreased NO levels may also suggest a probable role of NO in the adverse effect.

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Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats.

Cited by 248 publications

References 52 publications

Potential Benefits of Peroxynitrite

Potential Benefits of Peroxynitrite

Nitric Oxide and the Surgical Patient

Effects of electromagnetic radiation from a cellular telephone on the oxidant and antioxidant levels in rabbits

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