Post-ischemic Treatment with Candesartan Protects from Cerebral Ischemic/ Reperfusion Injury in Normotensive Rat

Large body of evidences has indicated that the renin – angiotensin system (RAS) and its effector peptide Angiotensin II may be involved in the pathophysiology of stroke. Previous studies showed that preischemic RAS inhibition reduced brain injury but effects of post-ischemic RAS inhibition on ischemic/reperfusion injuries have not completely been elucidated. Therefore, the present study has investigated the effects of post-ischemic AT1 receptor blocked with candesartan treatment on cerebral infarction and motor function following transient focal cerebral ischemia in normotensive rats. Male normotensive rats were studied in three groups as sham, ischemic control and ischemic group which received candesartan (0.3mg/kg) at the beginning of reperfusion period. Transient focal cerebral ischemia was induced by 90 min occlusion of the left middle cerebral artery, followed by 24 hr reperfusion. Neurological deficit score (NDS ) evaluated at the end of the reperfusion period. Total, cortical and striatal infarct volumes were determined using TTC staining technique. Animals in sham group had normal motor function and no ischemic lesions were observed in their cortical or striatal regions. MCAO in control ischemic group produced considerable infarctions in cortex and striatum in conjunction with severe impaired motor functions. AT1 receptor blocked with candesartan significantly reduced infarct volumes in the cortex and the striatum with improvement in NDS compared to control ischemic group. In conclusion, the results of the present study indicated that AT1 receptor blocked with candesartan can decrease ischemic brain injury and improve neurological outcome. Keyword: RAS, Candesartan, AT1 receptor, Focal cerebral ischemia, Rat.