title: Effects of ATP-sensitive potassium channel blockers on vascular hyporeactivity, mesenteric blood flow, and survival in lipopolysaccharide-induced septic shock model.
abstract: In this study, the possible therapeutic effects of various ATP-sensitive potassium channel (KATP) blockers (glibenclamide, repaglinide, 5-HD, HMR-1098) have been tested in experimental septic shock model. Rats were given lipopolysaccharide (1 mg·kg(-1)) to create experimental shock model and 4 h later, under 400 mg·kg(-1) chloral hydrate anesthesia, parameters such as blood pressure, mesenteric blood flow, the response of mesenteric circulation to phenylephrine (vasoconstrictor stimulation), and organ and oxidative damage were analyzed. Also 75 mg·kg(-1) lethal dose of lipopolysaccharide was given to mice and effects of KATP blockers on survival have been tested. Non-selective blocker glibenclamide with sulphonylurea structure and sarcolemmal KATP channel blocker HMR-1098, which have the similar chemical structure, have improved the pathological parameters such as decrease in mesenteric blood flow, vascular hyporeactivity, but could not prevent the decrease in blood pressure, and oxidative and organ damage that were observed in the shock model. Also, both blockers have decreased the mortality rate from 80% to 40%-50%. Similar (preventive) therapeutic effects were not observed with non-selective blocker repaglinide and mitochondrial KATP channel blocker 5-HD, which were non-sulphonylurea structure. As a result, only KATP channel blockers that have sulphonylurea structure can be a new therapeutic approach in septic shock.
authors.affiliation: a Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Boz
authors.affiliation: b Department of Histology and Embryology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Pergin
authors.initials: P
authors.lastname: Atilla
authors.affiliation: a Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Alper B
authors.initials: AB
authors.lastname: Iskit
authors.affiliation: a Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ilhan
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D054086:KATP Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate / Q000639:trends; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D054086:KATP Channels; D008070:Lipopolysaccharides; D026902:Potassium Channel Blockers
keywords: 5-HD; HMR-1098; KATP channel blockers; bloqueurs du canal KATP; choc septique; glibenclamide; repaglinide; septic shock