Evidence of hydroxyl free radical generation by calcium overload in rat myocardium.
Although calcium (Ca2+) is important in cardiac dysfunction and has also been reported as a source of oxidative toxicity, the connection between Ca2+ overload and oxygen free radicals in the myocardium is not clear. We have investigated whether Ca2+ overload generates hydroxyl free radicals in rat ventricle. HPLC with electrochemical detection was used to measure the levels of 2,3- and 2,5-dihydroxybenzoic acid (DHBA) formed when the hydroxyl free radical reacts with salicylate. Ringer's solution containing salicylic acid (0.5 nmol microL-1 min-1) was infused through a microdialysis probe in the region of the left anterior descending coronary artery of the rat ventricle. A positive linear correlation was obtained between Ca2+ and hydroxyl free radical formation trapped as 2,3-DHBA (r2 = 0.976) and 2,5-DHBA (r2 = 0.982) in the myocardial dialysate. The administration of ouabain (1 mg kg-1, i.v.), a Ca2+ elevator, into the femoral vein significantly increased the level of 2,3- and 2,5-DHBA. These results indicate that Ca2+ overload generates hydroxyl free radicals in rat heart.
Obata
T
T
Department of Pharmacology, Oita Medical University, Japan.
Tamura
M
M
Yamanaka
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000633:toxicity*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005841:Gentisates; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D006900:Hydroxylation; D008297:Male; D017551:Microdialysis; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000378:metabolism; D020156:Salicylic Acid
D002316:Cardiotonic Agents; D005841:Gentisates; D062385:Hydroxybenzoates; D012459:Salicylates; D017665:Hydroxyl Radical; D010042:Ouabain; C009135:2,3-dihydroxybenzoic acid; D006899:Mixed Function Oxygenases; D020156:Salicylic Acid; D002118:Calcium; C010925:2,5-dihydroxybenzoic acid