Peroxide-cyclooxygenase interactions in postasphyxial changes in retinal and choroidal hemodynamics.
To test the role of reactive oxygen species and cyclooxygenase products in the retinal hemodynamic changes induced by asphyxia, we measured retinal (RBF) and choroidal blood flows (ChBF), malondialdehyde (MDA), prostaglandin E2 (PGE2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TxB2) in 1- to 3-day-old pigs treated with saline, the free radical scavengers U-74389F or high-dose allopurinol, the cyclooxygenase inhibitors ibuprofen or indomethacin, or the thromboxane synthase blocker CGS-13080 before and 5 and 60 min after a 5-min period of asphyxia. In saline-treated animals, RBF and ChBF increased 5 min after asphyxia and decreased at 60 min. The increases in RBF and ChBF at 5 min postasphyxia were slightly attenuated by cyclooxygenase blockers and free radical scavengers but not by thromboxane synthase inhibition, whereas all drugs prevented the decreases at 60 min. MDA, TxB2, PGE2, and 6-keto-PGF1 alpha increased 5 min after asphyxia; at 60 min, PGE2 and 6-keto-PGF1 alpha returned to nearly preasphyxial levels, but MDA and TxB2 continued to increase. Cyclooxygenase inhibition prevented the asphyxia-induced rise in MDA, and the free radical scavengers prevented that of prostanoids. In isolated eyecup preparations, H2O2 and cumene hydroperoxide constricted retinal arteries; this effect was blocked by cyclooxygenase and thromboxane synthase inhibitors. The data suggest that during oxidative stresses reactive oxygen species are generated from the cyclooxygenase pathway and, in turn, also activate the synthesis of thromboxane; the latter mediates the oxidative stress-induced ocular vasoconstriction that might trigger the neovascularization of retinopathy of prematurity.
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Department of Pediatrics, University of Montreal, Québec, Canada.
Hardy
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Abran
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Li
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Peri
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Cuzzani
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Varma
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D015104:3,4-Methylenedioxyamphetamine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001237:Asphyxia / Q000378:metabolism*; D002829:Choroid / Q000098:blood supply* / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D010545:Peroxides / Q000378:metabolism*; D011281:Pregnatrienes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011460:Prostaglandins F / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012160:Retina / Q000378:metabolism*; D012171:Retinal Vessels / Q000187:drug effects*; D012965:Sodium Chloride / Q000494:pharmacology; D013552:Swine
D000975:Antioxidants; D016166:Free Radical Scavengers; D010545:Peroxides; D011281:Pregnatrienes; D011460:Prostaglandins F; D017382:Reactive Oxygen Species; C074965:U 74389F; D012965:Sodium Chloride; D015104:3,4-Methylenedioxyamphetamine; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone