Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells.

Weiss, Stephen J.; Young, Judy; LoBuglio, Albert F.; Slivka, Adam; Nimeh, N.

doi:10.1172/jci110307

Cited by 537 publications

(200 citation statements)

References 31 publications

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“…The precise mechanism via which an inflammatory response would up regulate a K+ channel-mediated backup relaxation mechanism is unclear. Activated granulocytes, however, may cause endothelial cell damage due to the release of superoxide radicals (Sacks et al, 1978;Weiss et al, 1981) which are known to inactivate NO (Gryglewski et al, 1986;Chen & Gillis, 1991). Consequently a decrease in NO-mediated relaxation, as observed in pulmonary veins from short-term pulmonary hypertensive sheep where ionomycin-mediated relaxations tended to be attenuated, may result in a greater contribution ofK+ channel-mediated mechanisms to endothelium-dependent relaxation.…”

Section: Vasodilator Responsesmentioning

confidence: 99%

Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by N^G‐nitro‐L‐arginine in pulmonary hypertension

Kemp¹,

Smolich²,

Ritchie³

et al. 1995

British J Pharmacology

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1 The effect of the nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NOARG), on endotheliumdependent relaxation to a receptor-independent agent, ionomycin, was examined in isolated pulmonary arteries and veins from control, short-term and chronic pulmonary hypertensive sheep. All vessel segments were contracted to optimal levels of active force with endothelin-I to record endotheliumdependent relaxation. 2 Pulmonary hypertension was induced by continuous pulmonary artery air embolization for 1 day (short-term) and 14 days (chronic) and was associated with a 2 and 3 fold increase in pulmonary vascular resistance respectively.3 L-NOARG (0.1 mM) reduced the maximum relaxation (Rm,) to ionomycin in large and mediumsized pulmonary arteries from control sheep by approximately 70%. By contrast, L-NOARG (0.1 mM) did not inhibit the Rmax to ionomycin in matched vessels from short-term and chronic pulmonary hypertensive sheep. 4 Resistance of ionomycin-induced relaxations to inhibition by L-NOARG, was confined to the arterial vasculature in chronic pulmonary hypertensive animals, as relaxations to ionomycin in large and medium-sized chronic pulmonary hypertensive veins were, like those in control veins, abolished by L-NOARG. Both large and medium-sized pulmonary veins from short-term pulmonary hypertensive sheep, however, were resistant to block by L-NOARG.5 Neither sensitivity (pEC5o) nor RmS, to ionomycin in large, short-term pulmonary hypertensive arteries was affected when the extracellular concentration of K+ was increased isotonically to 30 mm. Nifedipine (0.3 gM) was present throughout to prevent high K+-induced smooth muscle contraction. In the presence of this high extracellular K+, however, L-NOARG (0.1 mM) caused complete inhibition of the relaxation to ionomycin, whereas in normal extracellular K+ (4.7 mM), L-NOARG only weakly inhibited ionomycin relaxations. 6 In conclusion, the onset of pulmonary hypertension in sheep following air embolization, is associated with the development of resistance of endothelium-dependent relaxations to block by L-NOARG. The mechanism of L-NOARG resistance appears to be due to the up-regulation of a K+ channel-mediated backup vasodilator mechanism which can compensate for the loss of nitric oxide (NO)-mediated relaxation. Although this mechanism remains functionally 'silent' in the presence of NO it is able to maintain adequate endothelium-dependent vasodilatation during pulmonary hypertension if NO synthesis is compromised.

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Section: Vasodilator Responsesmentioning

confidence: 99%

Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by N^G‐nitro‐L‐arginine in pulmonary hypertension

Kemp¹,

Smolich²,

Ritchie³

et al. 1995

British J Pharmacology

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“…However, the ability of neutrophils and macrophages to induce injury in other cells in vitro [10][11][12] suggests that these early stages of muscle inflammation may also involve damage to muscle fibers caused by the invading cells. This possibility is supported by the ability of neutrophils to induce skeletal muscle injury during tissue reperfusion after ischemia [13,14].…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

Pizza

Hernandez

Tidball

1998

Journal of Leukocyte Biology

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The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1 ؉ and ED2 ؉ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor N -nitro-L-arginine methyl ester (L-NAME) significantly reduced the concentrations of neutrophils, ED1 ؉ and ED2 ؉ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for L-NAME-treated animals compared with watertreated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between L-NAME-treated and control animals, suggesting that L-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells.

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“…Jones et al (1994), demonstrated that homocysteine generated oxygen free radicals by observing the toxic effects of homocysteine independently and in the presence of Cu 2+ , and their correlation with increased lipid peroxidation, which was inhibited by catalase and attenuated by desferal. Oxygen radicals have been shown to cause endothelial injury (Weis et al 1981;Sacks et al 1978;Crapo, 1986;Kapoor and Prasad, 1994). The oxidative hypothesis of atherosclerosis is based upon oxidative stress induced endothelial injury (Henriksen et al 1981).…”

Section: Homocysteine and Atherosclerosismentioning

confidence: 99%

Homocysteine and Malondialdehyde as Predictors of Restenosis Following Percutaneous Coronary Intervention

et al. 2006

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Restenosis is one of the major adverse outcomes of Percutaneous CoronaryIntervention (PCI). Previous studies have shown conflicting reports for homocysteine as a predictor of restenosis following PCI. The conflicting reports may be due to oxidative factors (stimulation of polymorphonuclear leukocyte [PMNL]-induced reactive oxygen species generation, xanthine-xanthine oxidase, and arachidonic acid metabolism) other than homocysteine which could cause endothelial cell dysfunction leading to restenosis.Malondialdehyde (MDA), a lipid peroxidation product, is a marker for oxidative stress and is related to all oxidative factors. Therefore, it is possible that serum MDA may be a better predictor of restenosis than plasma homocysteine. The purpose of this study is to determine whether or not the pre-procedural serum MDA and plasma homocysteine levels are elevated in patients who develop restenosis post PCI.The study included fifty-one patients undergoing elective PCI who consented to participate in a protocol that was approved by the Ethics Committee of the University of Saskatchewan. Homocysteine and malondialdehyde were measured in the plasma and serum respectively. Blood samples were collected pre-procedural, 0 time, 8 hours, 24 hours, and 6 months post-procedure. Exercise tolerance tests were performed at two weeks, and six months post-procedure to determine if there was any evidence of restenosis.The results of the study showed that pre-procedural values of plasma homocysteine in the restenosis and non-restenosis groups were 10.37 ± 0.46 and 10.73 ± 0.49 respectively. These values were not significantly different (p=0.60) between the groups. The pre-procedural levels of plasma homocysteine were not significantly ii different (p=0.08) from the post-PCI values of those patients who did not develop restenosis at the 6-month time interval. However, the pre-procedural levels of plasma homocysteine were significantly different from the post-PCI values of those patients in the restenosis group at the 24hr (p=0.04) and 6-month (p=0.002) time intervals. In the restenosis group there was a significant increase (24%) after six months in the values of homocysteine from the pre-procedural levels. Thus, this indicates that restenosis is associated with higher post-PCI levels of homocysteine.The pre-procedural levels of serum MDA in the restenosis and non-restenosis groups were 0.124± 0.16 and 0.147± 0.02 respectively. There was no significant difference (p=0.60) between the two groups. There was also no significant difference The results suggest that pre-procedural levels of plasma homocysteine and serum MDA were not predictors of restenosis following PCI. However, the post-PCI sixmonth levels of both homocysteine and MDA are predictors of restenosis. Moreover, the post-PCI levels of MDA were better predictors of restenosis than the post-PCI levels of homocysteine because the increase in MDA levels were greater at six months than the rise in homocysteine levels at the same time interval.iii ACKNOWLEDGEMENTS

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Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells.

Cited by 537 publications

References 31 publications

Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by N^G‐nitro‐L‐arginine in pulmonary hypertension

Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by N^G‐nitro‐L‐arginine in pulmonary hypertension

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

Homocysteine and Malondialdehyde as Predictors of Restenosis Following Percutaneous Coronary Intervention

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Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells.

Cited by 537 publications

References 31 publications

Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by NG‐nitro‐L‐arginine in pulmonary hypertension

Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by NG‐nitro‐L‐arginine in pulmonary hypertension

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

Homocysteine and Malondialdehyde as Predictors of Restenosis Following Percutaneous Coronary Intervention

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Product

Resources

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Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by N^G‐nitro‐L‐arginine in pulmonary hypertension

Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by N^G‐nitro‐L‐arginine in pulmonary hypertension