Angiotensin-converting enzyme inhibitors reduce oxidative stress intensity in hyperglicemic conditions in rats independently from bradykinin receptor inhibitors

Abstract

Aim

To investigate whether bradykinin-independent antioxidative effects of angiotensin-converting enzyme inhibitors (ACEIs) exist in acute hyperglycemia.

Methods

Male Wistar rats were divided into the normoglycemic group (n = 40) and the hyperglycemic group (n = 40). Hyperglycemia was induced by a single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) dissolved in 0.1 mol/L citrate buffer (pH 4.5) 72 hours before sacrifice. The normoglycemic group received the same volume of citrate buffer. Each group was divided into five subgroups (n = 8): control group, captopril group, captopril + bradykinin B1 and B2 receptor antagonists group, enalapril group, and enalapril + bradykinin B1 and B2 receptor antagonists group. Captopril, enalapril, B1 and B2 receptor antagonists, or 0.15 mol/L NaCl were given at 2 and 1 hour before sacrifice. Oxidative status was determined by measuring the concentration of malondialdehyde and H ₂O ₂, and the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).

Results

In STZ-induced hyperglycemic rats ACEIs significantly reduced H ₂O ₂ and MDA concentration, while they significantly enhanced SOD and GPx activity. The hyperglycemic group treated simultaneously with ACEIs and bradykinin B1 and B2 receptor antagonists showed a significant decrease in H ₂O ₂ concentration compared to the control hyperglycemic group.

Conclusion

These results suggest the existence of additional antioxidative effect of ACEIs in hyperglycemic conditions, which is not related to the bradykinin mediation and the structure of the drug molecule.