Protective effect of diltiazem on myocardial ischemic injury associated with .OH generation.
We examined the protective effect of diltiazem, a calcium antagonist, on myocardial ischemic injury associated with generation of hydroxyl free radicals (.OH). Salicylic acid in Ringer's solution (0.5 nmol.microliter-1.min-1) was infused directly through a microdialysis probe to detect the generation of .OH as reflected by the formation of 2,3-dihydroxybenzoic acid (DHBA) in the myocardium. Cardiac dialysate was assayed for 2,3-DHBA by a high-performance liquid chromatographic-electrochemical (HPLC-EC) procedure. The heart was subjected to myocardial ischemia for 15 min by occlusion of left anterior descending artery (LAD). The presence of .OH was indicated in the ischemic reperfused rat heart. However, when heart was reperfused, the elevation of 2,3-DHBA by 15-min ischemia was not observed in the ischemic zone following systemic administration of diltiazem (100 micrograms.min-1.kg-1), a calcium antagonist. When corresponding experiments were performed with allopurinol (10 mg.kg-1) administration of i.v. injection, the elevation of 2,3-DHBA was not observed. These results suggest that diltiazem may suppress the .OH generation from xanthine-xanthine oxidase system by ischemia-reperfusion.
Obata
T
T
Department of Pharmacology, Oita Medical University, Japan.
Yamanaka
Y
Y
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000378:metabolism; D020156:Salicylic Acid; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D002121:Calcium Channel Blockers; D062385:Hydroxybenzoates; D012459:Salicylates; D014970:Xanthines; D019820:Xanthine; D017665:Hydroxyl Radical; D000493:Allopurinol; C009135:2,3-dihydroxybenzoic acid; D014969:Xanthine Oxidase; D004110:Diltiazem; D020156:Salicylic Acid; D009638:Norepinephrine