Pretreatment with candesartan protects brain against ischemia in normotensive rats / 药物分析学报

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.