Blood vessels convert arachidonic acid to prostacyclin (PGI(,2)), which is a potent inhibitor of platelet aggregation and thrombus formation. Polyunsaturated fatty acids (PUFA) or their hydroperoxy metabolites can cause a reduction in PGI(,2) production. Therefore, in the present study, the metabolism of PUFA and their effects on PGI(,2) production have been investigated. / Linoleic acid is converted by aorta to hydroperoxy metabolites, which are either dehydrated to oxo compounds, reduced to monohydroxy products, or converted to epoxyhydroxy-octadecenoic acids. The latter are then hydrolyzed to trihydroxy metabolites by aortic epoxide hydrolases. Aorta also converts eicosatrienoic acid to similar products, which are formed via 12-hydroperoxy-8,10-heptadecadienoic acid. / GC-MS analysis indicated that the major oxygenated PUFA metabolite formed by rat and bovine blood vessels was 6-oxoprostaglandin-F(,1(alpha)). Substantial amounts of free and esterified monohydroxy and trihydroxy metabolites of linoleic acid were detected, especially in rat and rabbit aortae. Reduction of glutathione peroxidase activity by administration of a selenium-deficient diet had no significant effect on the formation of any of the above products. / The presence of esterified monohydroxy and trihydroxy PUFA metabolites in aortic lipids indicates that their esterified hydroperoxy precursors are present. An excess of these products could inhibit PGI(,2) synthesis and contribute to the onset of atherosclerosis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.72056 |
| Date | January 1985 |
| Creators | Funk, Colin D. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000222598, proquestno: AAINL24058, Theses scanned by UMI/ProQuest. |
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