Endogenous reactive oxygen mediate sublethal endothelial during reoxygenation metabolites cell dysfunction

Purpose: Endothelial cells (EC) secrete vasoactive eicosanoids, which maintain organ blood flow. Because EC are a major source ofeicosanoids, we studied the effects ofreoxygenation on EC prostacyclin production. Methods: Bovine aortic EC cultures were exposed to 2 hours of normoxia, then 1 hour of hypoxia (Po 2 = 10 -+ 3.5 mm Hg), followed by 1.5 hours of reoxygenation in either normal medium or medium plus either superoxide dismutase (SOD, 300 units/ml), catalase (1200 units/ml), allopurinol (5.0 x 10-* mol/L), or dinitrophenol (10-4 mol/L). Results: Prostacyclin production decreased to 40% (p 85%, p < 0.05) sustained recovery of basal prostacyclin production at 30, 60, and 90 minutes of experimental reperfusion. Conclusions: The hypoxia-induced decrease in EC prostacyclin does not recover during reoxygenation. Catalase/SOD allowed return to baseline prostacyclin production during reoxygenation, implicating reactive oxygen metabolites as mediators of decreased eicosanoid biosynthesis. Recovery of prostacyclin production after 60 minutes reoxygenation with dinitrophenol but not allopurinol suggests a mitochondrial origin of the oxygen metabolites responsible for decreased prostacyelin biosynthesis. (J VAsc SURG 1996;23:95-103.)

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