Cardiac microdialysis of salicylic acid .OH generation on nonenzymatic oxidation by norepinephrine in rat heart.
The effect of pargyline, a monoamine oxidase inhibitor, on the generation of hydroxyl free radicals (.OH) was investigated using cardiac microdialysis. Salicylic acid in Ringer's solution (0.5 nmol x microL(-1) x min(-1)) 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 rats. When pargyline (100 nmol x microL(-1) x min(-1)) was infused in rat heart, the level of norepinephrine (NE) gradually increased in a time-dependent manner and an increase of DHBA was also observed. When NE was administered to the pargyline pretreated animals, a marked elevation in the levels of 2,3- and 2,5-DHBA formation was obtained, as compared to the group treated with NE only, showing a positive linear correlation between NE and .OH formation trapped as 2,3-DHBA (R2 = 0.981) or 2,5-DHBA (R2 = 0.984) in the dialysate. NE clearly produced an increase in .OH formation. These results indicate that accumulation of NE in the extracellular fluid elicited by pargyline can be auto-oxidized, which in turn, leads (possibly by an indirect mechanism) to the formation of cytotoxic .OH free radicals.
Obata
T
T
Department of Pharmacology, Oita Medical University, Hasama-machi, Japan.
Yamanaka
Y
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005841:Gentisates; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D017551:Microdialysis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid
D005841:Gentisates; D062385:Hydroxybenzoates; D008996:Monoamine Oxidase Inhibitors; D012459:Salicylates; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D010293:Pargyline; D020156:Salicylic Acid; C010925:2,5-dihydroxybenzoic acid; D009638:Norepinephrine