Acute-Microvascular-Injury Mechanisms

Marshall, J. Jeffrey; Kontos, Hermes A.

doi:10.1007/978-1-4612-0403-9_22

Cited by 1 publication

(3 citation statements)

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“…Our results confirm and extend previous studies showing that SODinhibitable superoxide production plays a key role in cerebral endothelial dysfunction after H/R. 10,17 It appears that peroxynitrite (ONOO Ϫ ) might be the secondary mediator responsible for impaired vasodilation to Ach after H/R. This is based on the data that ebselen, the membrane-permeable ONOO Ϫ scavenger, 29 substantially preserved dilator response to H/R, suggesting that ONOO Ϫ is a participant in H/R-induced endothelial dysfunction.…”

Section: Discussionsupporting

confidence: 82%

“…36 Thus, an alternative explanation of our findings is that superoxide generated by vascular NADPH oxidase, with subsequent formation of ONOO Ϫ , mediates cerebral endothelial dysfunction. Although H 2 O 2 and OH Ϫ take part in alteration of vascular function in other cerebral vessels, 10,37,38 our data with catalase and deferoxamine suggest that these radicals are not critical for H/R-impaired vasodilation in this model. These divergent results may be largely caused by using different animals or experimental models, the complexity of regulatory mechanisms involving ROS, and the heterogeneity of vascular endothelium.…”

Section: Discussionmentioning

confidence: 80%

“…16 It has been demonstrated that the formation of ROS after ischemia/reperfusion occurs in the brain and affects cerebral vascular tone. 9,10,[17][18][19] However, cellular mechanisms underlying H/R-induced cerebral vascular injury have not been well-defined.…”

mentioning

confidence: 99%

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NF-κB Activation Plays a Role in Superoxide-Mediated Cerebral Endothelial Dysfunction After Hypoxia/Reoxygenation

Xie

Ray

Short

2005

Stroke

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Background and Purpose-Cerebral vascular injury occurs in response to hypoxia/reoxygenation (H/R). However, the cellular signaling pathways that regulate this event remain unclear. The present study was designed to determine whether reactive oxygen species (ROS) mediate endothelial dysfunction after H/R in cerebral resistance arteries and, if so, the relative contribution of ROS, NADPH oxidase, and a nuclear factor-B (NF-B) pathway. Methods-Arterial diameter and intraluminal pressure were simultaneously measured on rat posterior cerebral arteries (PCA). Superoxide was measured by 5-mol/L lucigenin-enhanced chemiluminescence. Results-Hypoxia/reoxygenation selectively inhibited cerebral vasodilation to the endothelium-dependent agonist acetylcholine (Ach) (0.01 to 10 mol/L) by Ϸ50%. Impaired vasodilation after H/R was reversed by 2,2,6,6-tetramethylpiperidine-N-oxyl (Tempo) (100 mol/L), a cell-permeable superoxide dismutase mimetic, and partially by ebselen (10 mol/L), a peroxynitrite scavenger. H/R-impaired vasodilation to Ach was also preserved by apocynin (1 mmol/L), a specific inhibitor for NADPH oxidase. Correspondingly, H/R significantly increased lucigenin-detectable superoxide, which was reduced by either Tempo or apocynin, but not by allopurinol (10 mol/L), an inhibitor of xanthine oxidase. Finally, the NF-B inhibitors helenalin (10 mol/L) and MG-132 (1 mol/L) independently antagonized H/R-impaired Ach-induced vasodilation without affecting dilator response to sodium nitroprusside, an endothelium-independent vasodilator. Conclusions-These results indicate that superoxide mediates cerebral endothelial dysfunction after hypoxia/reoxygenation largely via activation of NADPH oxidase and possibly activation of NF-B pathway.

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Section: Discussionsupporting

confidence: 82%