Pretreatment with candesartan protects brain against ischemia in normotensive rats / 西安交通大学学报·英文版

ABSTRACT

Objective: Angiotensin II (Ang-II) increases NADPH oxidase activity and stimulates the production of reactive oxygen species (ROS) including superoxide anion through Ang II AT1-receptor (AT1-R) activation. ROS is involved in various pathological processes in brain ischemia. We investigated whether the AT1-R blocker (ARB) candesartan can protect normotensive rats against brain ischemia. Methods: After 2-week pretreatment with candesartan, rats were subjected to 2 hours middle cerebral artery occlusion-reperfusion (MCAO-R) and 24 hours later, the infarct volume, iNOS, and eNOS mRNA in the internal carotid artery was recorded and compared. Results: Candesartan pretreatment reduced cerebral ischemia and oxidative brain damage after MCAO-R in normotensive rats, resulting in a decreased cortical infarct volume [0.5 mg/kg candesartan, (46.8±13.2) mm3; 1.0 mg/kg candesartan, (19.3±15.3) mm3 vs. control, (111.7±14.3) mm3; P<0.05, P<0.01, respectively]. Candesartan pretreatment increased the eNOS mRNA level in the internal carotid artery. Conclusion: In normotensive rats exposed to MCAO-R, candesartan protectes against brain ischemia. This effect may represent a significant therapeutic advantage and may induce end-organ protection even at normal blood pressure.