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 microl(-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 (II) was administered to the MPP+ -pre-treatment group, the same results were obtained: a positive linear correlation (R2 = 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.
Obata
T
T
Department of Pharmacology, Oita Medical University, Japan. tobata@oita-med.ac.jp
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D015259:Dopamine Agents; D007093:Imidazoles; D048289:Imidazolidines; D020011:Protective Agents; D017665:Hydroxyl Radical; D015655:1-Methyl-4-phenylpyridinium; C078006:imidaprilat