Enalapril and captopril enhance glutathione-dependent antioxidant defensesin mouse tissues

The effect of enalapril and captopril on total glutathione content (GSSG GSH) and selenium-dependent glutathione peroxidase (Se-GPx) and glutathione reductase (GSSG-Rd) activities was investigated in mouse tissues. CF-1 mic e (4-mo-old females) received water containing enalapril (20 mg/l) or capto pril (50 mg/l) for 11 wk. Enalapril increased GSSG + GSH content (P < 0.05) in erythrocytes (147%), brain (112%), and lung (67%), and captopril increa sed GSSG + GSH content in erythrocytes (190%) and brain (132%). Enalapril e nhanced Se-GPx activity in kidney cortex (42%) and kidney medulla (23%) and captopril in kidney cortex (30%). GSSG-Rd activity was enhanced by enalapr il in erythrocytes (21%), brain (21%), liver (18%), and kidney cortex (53%) and by captopril in erythrocytes (25%), brain (19%), and liver (34%). In v itro erythrocyte oxidant stress was evaluated by thiobarbituric acid-reacti ve substances (TBARS) production (control 365 +/- 11, enalapril 221 +/- 26, captopril 206 +/- 17 nmol TBARS.g Hb(-1).h(-1); both P < 0.05 vs. control) and phenylhydrazine-induced methemoglobin (MetHb) formation (control 66.5 +/- 3.5, enalapril 52.9 +/- 0.4, captopril: 56.4 +/- 2.9 mu mol MetHb/g Hb; both P < 0.05 vs. control). Both angiotensin-converting enzyme inhibitor t reatments were associated with increased nitric oxide production, as assess ed by plasma NO, + NO, level determination (control 9.22 +/- 0.64, enalapri l 13.7 +/- 1.9, captopril 17.3 +/- 3.0 mu mol NO3- + NO2-/l plasma; both P < 0.05 vs. control). These findings support our previous reports on the ena lapril- and captopril-induced enhancement of endogenous antioxidant defense s and include new data on glutathione-dependent defenses, thus furthering c urrent knowledge on the association of ACE inhibition and antioxidants.