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dc.contributor.supervisorMink, Steven (Pharmacology and Therapeutics)en_US
dc.contributor.authorGotes Palazuelos, Jose
dc.date.accessioned2013-07-04T17:36:06Z
dc.date.available2013-07-04T17:36:06Z
dc.date.issued2013-07-04
dc.identifier.urihttp://hdl.handle.net/1993/21703
dc.description.abstractIn septic shock (SS), hydrogen peroxide (H2O2) and other reactive oxygen species (ROS) are released by inflammatory cells and have been implicated in tissue damage and inflammation. Recently, H2O2 has been established as an important signaling molecule and an important component of SS. The pathways involved in this process are not completely understood, but the formation of hydroperoxides (HPs), arachidonic acid (AA) metabolites and potassium (K+) channels have been implicated. In this study, we used a canine carotid ring preparation as a bioassay to determine the role of peroxyacetic acid (POX), a hydroperoxide (HP), in causing vasodilation and elucidate the subsequent pathways involved. We removed internal carotid artery segments from dogs and placed them in an organ bath. The segments were preconstricted after which we added POX to the preparation. We found that POX produced an endothelium and nitric oxide independent vasodilation in the carotid artery ring preparation. This decrease in tension could be prevented by high concentrations of K+ in the bath. This suggested that K+ channels were involved in POX’s action. Further investigation showed that the particular K+ channels implicated were the combination of small (SKCa) and intermediate conductance calcium activated K+ channels (IKCa). In addition we found that the prostaglandin H synthase (PGHS) inhibitor, indomethacin, could block POX’s mechanism of action. This finding indicates that PGHS takes part in the vasodilation caused by POX. Our results suggest that HPs that are released from inflammatory cells in sepsis could stimulate the PGHS pathway leading to prostaglandin synthesis and subsequently activating SKCa and IKCa to produce vasodilation. Inhibition of this pathway may be important component in the treatment of SS.en_US
dc.language.isoengen_US
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectsepsisen_US
dc.subjectvasodilationen_US
dc.subjecthydroperoxidesen_US
dc.subjectpotassium channelsen_US
dc.titleHydroperoxides and potassium channels: a possible mechanism for vasodilation in septic shock.en_US
dc.typeinfo:eu-repo/semantics/masterThesis
dc.typemaster thesisen_US
dc.degree.disciplinePharmacology and Therapeuticsen_US
dc.contributor.examiningcommitteeHalayko, Andrew (Physiology) Bose, Ratna (Pharmacology and Therapeutics)en_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.noteOctober 2013en_US


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