Role of candesartan against cerebral ischemia and oxidative damage in normotensive rats / 西安交通大学学报·英文版

ABSTRACT

Objective: Angiotensin II (Ang II) contributes to modulating blood pressure by stimulation of Ang II AT1 receptors. We devised a rat transient middle cerebral artery occlusion (MCAO) model to assess whether oxidative damage is decreased after pretreatment with Angiotensin II AT1 receptor blocker (ARB). Methods: After 2 weeks pretreatment with ARB 0.5 and 1 mg/kg, the male Wister rats were subjected to 2 h middle cerebral artery occlusion (MCAO). At 24 h, the lumen diameter of middle cerebral artery, the plasma level of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and HIF-1α levels were recorded and compared. Results: After pretreatment with ARB 0.5 and 1 mg/kg, blood pressure did not significantly change compared with that of controls. In the group of candesartan at 1 mg/(kg· day), the lumen diameter was significantly increased compared to that in control group [(86.0±5.0) μm vs. (69.0± 2.1) μm; P < 0.01, n = 6 - 8]. The plasma 8-OHdG levels of ARB pretreatment groups were decreased. In immunohistochemical findings, 8-OHdG- and HIF-1α-containing cells in ARB pretreatment groups were decreased. Conclusion: Brain ischemia and oxidative damage can be reversed by AT1 receptor blockade in normotensive rats after transient cerebral artery occlusion.