Print ISSN 2319-2003 | Online ISSN 2279-0780 doi: http://dx.doi.org/10.18203/2319-2003.ijbcp20150855 IJBCP International Journal of Basic & Clinical Pharmacology www.ijbcp.com International Journal of Basic & Clinical Pharmacology | September-October 2015 | Vol 4 | Issue 5 Page 853 Research Article Neuroprotective effect of renin angiotensin system blockers on experimentally induced Alzheimer’s disease in rats Wafaa A. Hewedy 1 , Wessam F. El-Hadidy 2 * INTRODUCTION Alzheimer’s disease (AD), the most common form of dementia, is an insidious, progressive disorder characterized by subtle behavioral and memory disturbances; progressing into global cognitive impairment, memory loss, behavioral and psychiatric disturbances, and functional impairment. 1 The greatest risk factor for the development of AD is advancing age. However, the exact mechanisms of AD are incompletely understood. 2 One of the key pathological features of AD is deposition of a 40-42 amino acid peptide called amyloid-β (Aβ). Aβ is the building brick for Aβ peptide (Aβ-P) that is deposited in the brain as extracellular senile plaques, or within the walls of the cerebrovasculature. 3 Development of drugs that reduce Aβ deposition through inhibition of its production or increased promotion of its removal is now a major therapeutic strategy. Much evidence points to a link between hypertension and AD. 4 High systolic blood pressure is reported to be associated with low brain weight, whereas a high systolic and diastolic blood pressure are associated with increased prevalence of the neurofbrillary tangles (NFT) in hippocampal brain regions. 5 Although the use of antihypertensive drugs has ABSTRACT Background: Alzheimer’s disease (AD) is a major world-wide health problem. Much evidence points to a link between hypertension and AD. However, the exact effects of different antihypertensive drugs on AD need to be more assessed. The aim was to evaluate and compare the possible effects of perindopril, and candesartan on cognitive impairment, oxidative stress markers, and brain concentrations of amyloid beta-peptide (Aβ-P) in a rat model of induced dementia. Methods: Thirty-two adult male Wistar rats were distributed among 4 groups; (1) normal controls; (2) rats with dementia induced by intracerebroventricular administration of streptozotocin (ICV-STZ) and received no treatment; (3) ICV-STZ rats treated orally with perindopril for 3 weeks; and (4) ICV-STZ rats treated orally with candesartan for 3 weeks. The assessed parameters were spatial memory by Morris Water Maze test, brain tissue level of total antioxidant capacity (TAC), reduced glutathione (GSH), lipid peroxidation product (malondialdehyde [MDA]), and Aβ-P. Results: Both perindopril and candesartan attenuated STZ-induced memory impairment, caused a signifcant increase in TAC and GSH levels, reduced MDA levels, whereas only candesartan signifcantly reduced Aβ-P levels. Conclusions: This study reports that candesartan and perindopril can reverse the free radical induced damages and resultant memory defects, and may suggest candesartan as worthy drugs for prevention of Aβ-P deposition in this animal model of AD. Keywords: Streptozotocin, Amyloid beta-peptide, Hypertension, Perindopril, Candesartan, Oxidative stress 1 Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt, 2 Department of Pharmacology and Experimental Therapeutics, Medical Research Institute, Alexandria University, Alexandria, Egypt Received: 24 August 2015 Accepted: 14 September 2015 *Correspondence to: Wessam F. El-Hadidy, Email: drwessamhadidy@ gmail.com Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.