Effects of ATP-sensitive potassium channel blockers on vascular hyporeactivity, mesenteric blood flow, and survival in lipopolysaccharide-induced septic shock model

In this study, the possible therapeutic effects of various ATP-sensitive potassium channel (K ATP ) 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 l...

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Bibliographic Details
Published in:Canadian journal of physiology and pharmacology 2016-08, Vol.94 (8), p.858-867
Main Authors: Boz, Mustafa, Atilla, Pergin, Iskit, Alper B, Ilhan, Mustafa
Format: Article
Language:English
Subjects:
5-HD
Adenosine triphosphatase
Adenosine triphosphate
Animals
ATP
Blood
Blood flow
Blood Flow Velocity - drug effects
Blood Flow Velocity - physiology
bloqueurs du canal K
Cardiovascular system
Causes of
channel blockers
choc septique
Dose-Response Relationship, Drug
Effects
glibenclamide
Health aspects
HMR-1098
KATP Channels - antagonists & inhibitors
KATP Channels - physiology
Lipopolysaccharides
Lipopolysaccharides - toxicity
Mesenteric Arteries - drug effects
Mesenteric Arteries - physiology
Mice
Potassium channel blockers
Potassium Channel Blockers - pharmacology
Potassium Channel Blockers - therapeutic use
Prognosis
Rats
Rats, Wistar
Regional Blood Flow - drug effects
Regional Blood Flow - physiology
repaglinide
Sepsis
Septic shock
Shock, Septic - chemically induced
Shock, Septic - drug therapy
Shock, Septic - mortality
Survival Rate - trends
Vasoconstriction - drug effects
Vasoconstriction - physiology
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Summary:In this study, the possible therapeutic effects of various ATP-sensitive potassium channel (K ATP ) 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 K ATP blockers on survival have been tested. Non-selective blocker glibenclamide with sulphonylurea structure and sarcolemmal K ATP 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 K ATP channel blocker 5-HD, which were non-sulphonylurea structure. As a result, only K ATP channel blockers that have sulphonylurea structure can be a new therapeutic approach in septic shock.
ISSN:0008-4212
1205-7541
DOI:10.1139/cjpp-2015-0381