ACE inhibitor and angiotensin type I receptor antagonist in combination reduce renal damage in obese Zucker rats

Background. In this study, we evaluated whether a combination of an angiotensin-converting enzyme (ACE) inhibitor, benazepril (B), with an angiotensin type I receptor antagonist (AT1RA), irbesartan (I), is as effective or more than drugs as monotherapy in controlling renal damage in obese Zucker rats (OZR), a model of metabolic syndrome. Methods. During six months, G1 (OZR receiving no treatment); G2 (OZR with B 10 mg/kg/day); G3 (OZR with I 50 mg/kg/day); and G4 (OZR with B 5 mg/kg/day + I 25 mg/kg/day). Kidneys were processed for light microscopy (LM) and immunohistochemistry, including antibodies against interstitial alpha-smooth-muscle-actin (alpha-SMA), plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-beta(1)(TGF-beta(1)), and collagen (COL) I, III, and IV. Results. All treated groups presented similar reduction in blood pressure compared with untreated OZR. However, animals from G4 (B + I) showed better control on proteinuria together with a higher creatinine clearance. Additionally, G4 showed a significant (P<0.05) lower kidney weight; smaller glomerular area; lower glomerulosclerosis score; lower percentage of tubular atrophy, interstitial fibrosis, and interstitial alpha-SMA; lower tubular PAI-1 score; lower percentage of COL 1, III, and IV in renal interstitium; and lower wall/lumen ratio in renal vessels, when compared with the other groups. OZR treated with B and/or I showed a better outcome (P<0.01) in the carbohydrate and lipid metabolism in comparison with untreated OZR. Conclusion. These results suggest that combined therapy using B and I is more effective than therapy with either drug at monotherapy for controlling renal damage in this animal model. In addition, data presented here reaffirm the benefit of interacting against renin-angiotensin-system (RAS) in the metabolic syndrome.