Release of isoprostanes by human pulmonary artery in organ culture: A cyclo-oxygenase and nitric oxide dependent pathway

Isoprostanes are prostaglandin(PG)-like compounds initially described as formed by a direct action of radicals on arachidonic acid. However, the isoprostane, 8-iso PGF(2 alpha), is released by platelets and monocytes by cyclo-oxygenase dependent pathways. The free radical NO can modulate arachidonic acid metabolism in some cells, but its potential role in isoprostane formation has not been studied. Using human pulmonary artery in organ culture (24 h), we therefore investigated the role of cyclo-oxygenase and NO in 8-iso PGF(2 alpha) release, In endothelium-denuded segments of pulmonary artery, the inflammatory agents tumor necrosis factor cu, interleukin-1 beta, interferon gamma, and lipopolysaccharide stimulated the release of PGE(2) and 8-iso PGF(2 alpha), which were attenuated in both cases by the cyclo-oxygenase inhibitor indomethacin. By contrast, the NO synthase inhibitor L-N-G-nitro-L-arginine methyl ester inhibited 8-iso PGF(2 alpha), but not PGE(2) release. Thus, we show for the first time that human pulmonary vessels can produce isoprostanes and that NO synthase and cycle-oxygenase pathways are involved in their release. (C) 1997 Academic Press.