Cardiac microdialysis of Salicylic Acid •OH generation on nonenzymatic oxidation by norepinephrine in rat heart

Abstract

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 • μL −1 • 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 • μL • 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 (R 2 = 0.981) or 2,5-DHBA (R 2 = 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.