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Purpose: Angiotensin II receptor blockers (ARBs) have been found to have antioxidant effects and to reduce vascular injury after stroke, but whether the two are causally related is unclear.
Methods: 40 hypertensive rats (SHR) were treated with either candesartan 1 mg/kg or saline after 3 hours of middle cerebral artery occlusion (MCAO) and were reperfused for 21 hours prior to sacrifice. An additional group (n=16), were treated with the SOD mimetic, tempol, for 2 weeks prior to the same procedure. After saline perfusion, brain tissue was collected for quantification of excess hemoglobin, and biochemical analyses.
Results: Treatment with tempol and candesartan significantly reduced the blood pressure, but the effect of tempol was less pronounced than candesartan. Candesartan 1mg/kg significantly reduced hemorrhagic transformation (HT) in SHR animals after stroke (p<0.05). Animals treated with tempol had significantly lower incidence of HT than controls and this was NOT further reduced by candesartan (p=0.01). Candesartan treatment significantly increased the expression of eNOS in stroked hemisphere (p<0.05) a response that was lost in those treated with tempol. In contrast, the p-eNOS /eNOS ratio was significantly increased in animals treated with candesartan and tempol combination, compared to either alone (p<0.5).
Conclusion: Acutely administered candesartan reduces HT in SHRs at 24 hours after MCAO by an antioxidant mechanism.