Effects of Dual RAAS Blockade with Candesartan and Perindopril on Functional Renal Tests in Streptozotocin Induced Diabetic Nephropathy
Journal Title: Macedonian Journal of Medical Sciences (MJMS) - Year 2013, Vol 6, Issue 3
Abstract
Background: Diabetic nephropaty (DN) occurs in approximately 40% of patients with diabetes mellitus, and is the most common cause of end-stage renal disease. The combination of ACE inhibitors with ARB could lead to a more effective inhibition of rennin angiotensin aldosterone system (RAAS). Aim: The present study was undertaken to evaluate the effects of dual RAAS blockade with ARB (candesartan) and ACE inhibitor (perindopril) in streptozotocin induced diabetic nephropathy versus ACE-inhibitor or ARB alone. Materials and Methods: Wistar rats (n=125), were used in this investigation. Diabetes was induced by streptozotocin (STZ) 60 mg/kg. The diabetic rats (n=100) were randomly assigned to receive vehicle, ARB-Candesartan (5 mg/kg/per d), ACE inhibitor-Perindopril (6 mg/kg/per d), or a combination of low dose Can+Per (2.5 mg/kg/per d and 3 mg/kg/per d) respectively, from weeks 4- 12. Results: Treatment with candesartan or perindopril as monotherapy, although significantly, only partially prevented the symptoms and signs of DN. Candesartan and perindopril were equally effective in treatment of DN. Combination therapy was more effective than monotherapy with either drug. Conclusion: The results from this study demonstrate that combination treatment with both ACE and ARB in low doses may offer synergistic blockade of the RAAS, not obtainable with either drug alone.
Authors and Affiliations
Jasmina Trojacanec| Department of Preclinical and Clinical Pharmacology with Toxicology, Medical Faculty, Skopje, Republic of Macedonia, Dimce Zafirov| Department of Preclinical and Clinical Pharmacology with Toxicology, Medical Faculty, Skopje, Republic of Macedonia, Krume Jakjovski| Department of Preclinical and Clinical Pharmacology with Toxicology, Medical Faculty, Skopje, Republic of Macedonia, Kalina Gjorgjievska| Department of Preclinical and Clinical Pharmacology with Toxicology, Medical Faculty, Skopje, Republic of Macedonia, Plamen Trojacanec| Department of Veterinary Surgery, Faculty for Veterinary Medicine, Skopje, Republic of Macedonia, Nikola Labacevski| Department of Preclinical and Clinical Pharmacology with Toxicology, Medical Faculty, Skopje, Republic of Macedonia
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