Comparison of inhibitory action of candesartan and enalapril on brain ischemia through inhibition of oxidative stress

The effects of an angiotensin II type 1 (AT1) receptor blocker (ARB) on ischemic brain damage induced by middle cerebral artery (MCA) occlusion were compared with those of an angiotensin converting enzyme (ACE) inhibitor. Treatment of male C57BL/6J mice with an ARB, candesartan, reduced the brain ischemic area and neurological deficit after MCA occlusion at a non-hypotensive dose. In contrast, an ACE inhibitor, enalapril, did not reduce the brain ischemic area, and neurological deficit even at a hypotensive dose. Candesartan improved the reduction of brain surface blood flow after MCA occlusion, and inhibited the increase in superoxide production both in the cortex and brain arterial wall at non-hypotensive and hypotensive doses. However, enalapril did not affect the changes in blood flow and superoxide production in the brain after MCA occlusion. AT2 receptor expression in the ischemic area was increased at 3 h after MCA occlusion by pretreatment with candesartan, but not that with enalapril. AT1 receptor expression was neither affected by candesartan nor by enalapril. These results suggest that candesartan attenuated ischemic brain damage, at least partly, through inhibition of oxidative stress.