Effects of pretreatment with angiotensin II type 1 receptor blocker on focal cerebral ischemia-reperfusion injury in mice with arteriosclerosis

Aim: To investigate the effects of the angiotensin II type 1 receptor (AT1) blocker on cerebral ischemia-reperfusion injury in mice with atherosclerosis. Methods: The experiment was done in the Center Laboratory of First Military Medical University from September 2003 to December 2004. Forty apolipoprotein E (apoE) knock out mice were assigned randomly into control group (n=20): They were treated with high cholesterol diet for ten weeks; Telmisartan pretreatment group (n=20): They were given high cholesterol diet for eight weeks, then telmisartan at a dose of 0.3 mg/kg per day mixing with the food for two weeks. After the raising for 10 days, at the same time to establish ischemia reperfusion brain injury models, ischemia for 1 hour and reperfusion for 23 hours. The detection of relative index: Blood pressure (BP) was detected by tail-sleeves methods; The area percentage of infarction was calculated by image analysis system; Death rate of the animals in the two groups; The nerve functional lesion score was as following: 0 points: no nerve functional lesion physical sign; 1 point: the weakening of myodynamia of right-frontier claw; 2 points: bend of body towards left; 3 points: rotatory toward left side; 4 points: without antomatic action; The water containing quantity of brain tissue was detected.The development condition of superoxide anion was observed under the fluorescence microscope. Results: Except the animals dead before the end of the experiment, 5 mice were dead in control group and 4 mice in telmisartan group. Fifteen mice in control group and sixteen mice in telmisartan group were involved in the result analysis. 1 The effect of telmisartan pretreatment on the blood pressure of the animals: Compared with the control group, the effect of telmisartan pretreatment on the blood pressure of the animals before and after ischemia and after reperfusion was insignificant [(101±3), (105±5); (87±6), (88±3); (93±5), (94±6)mm Hg, (P > 0.05)]. 2 The effect of telmisartan pretreatment on the infarct area:Constant white infarct focus appeared after ischemia reperfusion injury. Compared with control group, infarct area decreased in telmisartan pretreatment group, and the difference was significant (P < 0.05). 3 The effect of telmisartan pretreatment on the animal's death rate, nerve functional defect score and the water containing quantity of brain tissues: Compared with control group, the telmisartan pretreatment could decrease the animal's death rate, nerve functional defect score and the water containing quantity of brain tissues [46.67%, 31.13%; 2.75±0.20, 2.00±0.30; (83.29±0.45)%, (80.17±032)%, P < 0.05]. 4 The effect of telmisartan pretreatment on the brain blood stream: After the infarct of mesencephalic arteries, the brain blood stream all decreased to below the 20% of base line value in the focus center of infarct. The brain blood stream in pretreatment group after reperfusion was higher than that in control group (P < 0.05). The brain blood stream in semi-area opaca all deceased to below 50% of the base line value. From 30 minutes post-infarct to post-reperfusion, the brain blood stream in pretreatment group (P < 0.05). 5 The effect of telmisartan pretreatment on the oxygen stress:The development of infarct focus active oxygen increased while the development of active oxygen in telmisartan pretreatment group was insignificant. The activity of recovery corymase II decreased in telmisartan pretreatment group than that of control group [((0.512±0.030),(0.782±0.032) mkat/g, P < 0.05]. Conclusion: The pre-blockade of AT1 receptor can dwindle the infarct area of ischemical reperfusion injury in rats with atheroscherosis, decrease the brain edema and the animal's death rate, imrove nerve loss of function physical sign,and inhibit the development of superoxide anion and the increase of activities of recovery corymase II oxidase in order to reduce the level of brain injury.