title: Glibenclamide attenuates the antiarrhythmic effect of endotoxin with a mechanism not involving K(ATP) channels.
abstract: The role of K(ATP) channels in the antiarrhythmic effect of Escherichia coli endotoxin-induced nitric oxide synthase (iNOS) was examined in an anesthetised rat model of myocardial ischemia and reperfusion arrhythmia by using glibenclamide (1 mg kg(-1)), nateglinide (10 mg kg(-1)) and repaglinide (0.5 mg kg(-1)). Endotoxin (1 mg kg(-1)) was administered intraperitoneally 4 h before the occlusion of the left coronary artery and glibenclamide, nateglinide or repaglinide was administered 30 min before coronary artery occlusion. We also evaluated the effects of K(ATP) channel blockers and nonselective K(+) channel blocker tetraethylammonium (TEA) on cardiac action potential configuration in the atria obtained from endotoxemic rats. The mean arterial blood pressure of rats receiving endotoxin was lower during both the occlusion and reperfusion periods. Endotoxin significantly reduced the total number of ectopic beats and the duration of ventricular tachycardia. Glibenclamide, but not nateglinide and repaglinide, prevented the hypotension and antiarrhythmic effects of endotoxin. Atria obtained from endotoxin-treated rats had prolonged action potential duration. This effect was abolished with pretreatment of iNOS inhibitors, l-canavanine and dexamethasone and perfusion of glibenclamide, but not with TEA and non-sulfonylurea drug, nateglinide. We demonstrated that glibenclamide inhibits the antiarrhythmic effect of endotoxin and this effect does not appear to involve K(ATP) channels.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, 06100, Turkey. alperi@hacettepe.edu.tr
authors.forename: Alper B
authors.initials: AB
authors.lastname: Iskit
authors.forename: Ulkem
authors.initials: U
authors.lastname: Erkent
authors.forename: Mert
authors.initials: M
authors.lastname: Ertunc
authors.forename: M Oguz
authors.initials: MO
authors.lastname: Guc
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ilhan
authors.forename: Rustu
authors.initials: R
authors.lastname: Onur
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D019446:Endotoxemia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D005905:Glyburide / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017180:Tachycardia, Ventricular / Q000378:metabolism / Q000503:physiopathology; D019789:Tetraethylammonium; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000378:metabolism / Q000503:physiopathology; D018879:Ventricular Premature Complexes / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002219:Carbamates; D003510:Cyclohexanes; D008070:Lipopolysaccharides; D010880:Piperidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C482199:lipopolysaccharide, E coli O55-B5; D000077715:Nateglinide; D010649:Phenylalanine; D019789:Tetraethylammonium; C072379:repaglinide; D000255:Adenosine Triphosphate; D005905:Glyburide