Protective Effects of Angiotensin II AT1 Receptors Blockade against Brain Injury in Experimental Model of Stroke in Rat

Ischemic stroke remains the third leading cause of invalidism and death in industrialized countries. It is suggested that renin–angiotensin system (RAS) may contribute in stroke related pathogenic mechanisms and involve in the ischemic brain damage. This study designed to investigate the role of angiotensin II (Ang II) in conjunction with AT1 receptors in treatment of the brain injuries following transient focal cerebral ischemia in rats. Forty eight male Sprague-Dawley rats were studied in four groups. Sham group, ischemic control group and two ischemic groups that received candesartan (0.1mg/kg, or 0.5mg/kg) at the beginning of reperfusion period. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the middle cerebral artery, followed by 24 hours reperfusion. At the end of the reperfusion period, neurological deficit score (NDS) was performed. Total cortical and striatal infarct volumes were determined using triphenyltetrazolium chloride (TTC) staining technique. Animals in sham operated group had normal motor function and no ischemic lesions were observed in cortical or striatal regions. Occurring ischemia in ischemic control group that received vehicle produced considerable infarction in cortex (253±15mm3) and striatum (92±7mm3), as well as these animals had sever impaired motor dysfunctions. Blocking of AT1 receptors with candesartan (0.1mg/kg or 0.5mg/kg) improved neurological outcome and significantly lowered cortical and striatal infarct volumes relative to ischemic control group. The findings of the present study indicated that stimulation of AT1 receptors by Ang II involved in ischemia/reperfusion injuries and blocking of AT1 receptors can decrease ischemic brain injury and improve neurological outcome.