Protective effect of imidaprilat, a new angiotensin-converting enzyme inhibitor against 1-methyl-4-phenylpyridinium ion-induced •OH generation in rat striatum

We examined the antioxidant effects of angiotensin-converting enzyme inhibitor on 1-methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical (. OH) formation in extracellular fluid of rat striatum. Rats were anesthetized and sodium salicylate in Ringer's solution (0.5 nmol mu l(-1) min(-1)) was infused through a microdialysis probe to detect the generation of . OH, as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. MPP+ clearly produced an increase in . OH formation in a concentration-dependent manner. When imidaprilat was infused in MPP+-pre-treated animals, the formation of dopamine and 2,3-DHBA significantly decreased, as compared with that in the MPP+-only-treated group. We compared the ability of two non-SH-containing angiotensin-converting enzyme inhibitors (imidaprilat and enalaprilat) with an SH-containing angiotensin-converting enzyme inhibitor (captopril) to scavenge . OH. All three angiotensin-converting enzyme inhibitors were able to scavenge . OH generated by the action of MPP+. However, the changes produced by captopril and enalaprilat were not significant. When dopamine was administered to the MPP+-pre-treatment group, a marked elevation was observed, showing a positive linear correlation between dopamine and . OH formation (2,3-DHBA) in the dialysate. Moreover, when iron (IT) was administered to the MPP+-pre-treatment group, the same results were obtained: a positive linear correlation (R-2 = 0.989) between the release of dopamine and 2,3-DHBA (R2 = 0.989) in the dialysate. When corresponding experiments were performed with imidaprilat-pre-treated animals, the level of 2,3-DHBA decreased. These results suggested that angiotensin-converting enzyme inhibitors may protect against MPP+-induced . OH formation in the rat striatum. (C) 1999 Elsevier Science B.V. All rights reserved.