title: Cyclooxygenase-1 and prostacyclin production by endothelial cells in the presence of mild oxidative stress.
abstract: This study aimed at evaluating the relative contribution of endothelial cyclooxygenase-1 and -2 (COX-1 and COX-2) to prostacyclin (PGI(2)) production in the presence of mild oxidative stress resulting from autooxidation of polyphenols such as (-)-epigallocatechin 3-gallate (EGCG), using both endothelial cells in culture and isolated blood vessels. EGCG treatment resulted in an increase in hydrogen peroxide formation in human umbilical vein endothelial cells. In the presence of exogenous arachidonic acid and EGCG, PGI(2) production was preferentially inhibited by a selective COX-1 inhibitor. This effect of selective inhibition was also substantially reversed by catalase. In addition, EGCG caused vasorelaxation of rat aortic ring only partially abolished by a nitric oxide synthase inhibitor. Concomitant treatment with a selective COX-1 inhibitor completely prevented the vasorelaxation as well as the increase in PGI(2) accumulation in the perfusate observed in EGCG-treated aortic rings, while a selective COX-2 inhibitor was completely uneffective. Our data strongly support the notions that H(2)O(2) generation affects endothelial PGI(2) production, making COX-1, and not COX-2, the main source of endothelial PGI(2) under altered oxidative tone conditions. These results might be relevant to the reappraisal of the impact of COX inhibitors on vascular PGI(2) production in patients undergoing significant oxidative stress.
authors: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
authors: Alice
authors: A
authors: Toniolo
authors: Carola
authors: C
authors: Buccellati
authors: Christian
authors: C
authors: Pinna
authors: Rosa Maria
authors: RM
authors: Gaion
authors: Angelo
authors: A
authors: Sala
authors: Chiara
authors: C
authors: Bolego
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D014665:Vasodilator Agents; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2