Effect of thimerosal on arrhythmia induced by coronary ligation: the involvement of ATP-dependent potassium channels.
Thiol-modifying agents induce the release of nitric oxide (NO) from endothelial epithelium and the release of reactive oxygen free radicals in the vascular system. Moreover, thiol groups are essential for the functioning of the ATP dependent potassium channel (K-ATP). The effects of thiol-modifying agents and their molecular mechanisms on arrhythmia have not been widely studied. In this study, we investigated the effect of the hydrophilic SH-group-oxidizing substance thimerosal on the arrhythmia induced by reperfusion/ischemia after coronary artery ligation in rats. We studied the possible involvement of the K-ATP and NOS on the effect of thimerosal. Thimerosal pretreatment (3, 30 mg/kg dose iv. 10 minutes before coronary occlusion) significantly decreased the length of total arrhythmia, ventricular tachycardia, and the arrhythmia score. This effect of thimerosal was reversed by the K-ATP opener pinacidil but not by the K-ATP blocker glibenclamide. The inhibition of iNOS by L-NAME did not alter the antiarrhythmic effect of thimerosal. These data clearly suggest that the antiarrhythmic effect of thimerosal is dependent upon the blockage of K-ATP.
Bozdogan
Omer
O
Biology Department, Faculty of Arts and Sciences, Abant Izzet Baysal University, Bolu, Turkey.
Gonca
Ersöz
E
Nebigil
Melih
M
Tiryaki
Eylem Suveren
ES
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology*; D001794:Blood Pressure; D003331:Coronary Vessels / Q000601:surgery; D004562:Electrocardiography; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate; D008026:Ligation; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D020110:Pinacidil / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013849:Thimerosal / Q000494:pharmacology*
D006146:Guanidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011725:Pyridines; D013849:Thimerosal; C073896:N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine; D020110:Pinacidil; D000255:Adenosine Triphosphate; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester