Glibenclamide, an antagonist of ATP sensitive K+ channels, blocks free radical generation in the rat myocardium.
The present study examined the effect of glibenclamide, an ATP-sensitive K+ (K(ATP)) channels antagonist, on the potassium chloride (KCl)-induced hydroxyl free radical (.OH) generation. Sodium salicylate in Ringer's solution (0.5 nmol/microl per min) was infused directly through a microdialysis probe to detect the generation of .OH as reflected by the formation of dihydroxybenzoic acid (DHBA) in the myocardium of anesthetized rat. The high concentration of KCl (70 mM) significantly increased the level of 2,3- and 2,5-DHBA by the action of depolarization by KCl. However, in the presence of glibenclamide (10 microM), KCl failed to increase the 2,3- and 2,5-DHBA formation. Moreover, when allopurinol (10 mg/kg), a xanthine oxidase inhibitor, was administered by i.v. injection, the elevation of DHBA was not observed. These results suggest that openings of cardiac K(ATP) channel by depolarization evokes .OH generation via xanthine oxidase reaction.
Obata
T
T
Department of Pharmacology, Oita Medical University, Japan. tobata@oita-med.ac.jp
Yamanaka
Y
Y
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005841:Gentisates; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D062385:Hydroxybenzoates / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005609:Free Radicals; D005841:Gentisates; D062385:Hydroxybenzoates; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013395:Sucrose; D000493:Allopurinol; D011189:Potassium Chloride; C009135:2,3-dihydroxybenzoic acid; D005905:Glyburide; C010925:2,5-dihydroxybenzoic acid; D012980:Sodium Salicylate