ABSTRACT
Objective To investigate the protective effects of pretreatment with valsartan, an angiotensin Ⅱ type 1 receptor blocker, on the brain against ischemia-reperfusion (I/R) injury. Methods Thirty-six healthy male C57BL/6J mice aged 10-12 weeks weighing 20-25 g were randomly divided into 2 groups (n - 18 each): valsartan group (V) and control group (C). In group V valsartan 2 mg?kg-1 dissolved in 2.5% NaHCO3 100 ?l was given intraperitoneally (i.p. ) every day for 10 days before experiment while in group C 2.5% NaHCO3 100?l without valsartan was given. The animals were anesthetized with intraperitoneal pentobarbital 40 mg?kg-1. Middle cerebral artery occlusion (MCAO) was produced by inserting an 8-0 nylon thread with rounded end into the left internal carotid artery and advancing it cranially until resistance was felt. MCAO was maintained for 1 h. The nylon thread was then withdrawn for reperfusion. A laser doppler blood flow detector (Omegaflo FLO-C1, Omegawave Co, Netherlands) was used to detect local cerebral blood flow (LCBF) at central and marginal infarct area [LCBF (%) = LCBF during I/R / baseline LCBF ? 100% ]. The model of MCAO was considered established when LCBF at central infarct area was 20% lower than the baseline value. LCBF was measured 10 min before MCAO (T0, baseline), as soon as MCA was occluded (T1) at 10, 30, 50 min of ischemia (T2-4) and at 10, 30, 60 min of reperfusion (T5-7) . MAP was measured immediately before valsartan administration, at T0 and T5. Neurological function deficit (NFD) was evaluated and scored (0 = no deficit, 4 = worst result) at 23 h after reperfusion was started . After evaluation of NFD the animals were anesthetized again and killed. The brains were removed. Cerebral water content was measured [cerebral water content (%) = (wet weight - dry weight) / wet weight ? 100%]. Infarct area was measured. Mortality rate was recorded.Results Pretreatment with valsartan did not affect MAP significantly but significantly reduced infarct area, brain water content, NFD and mortality rate and improved focal cerebral blood flow after MCAO. Conclusion Valsartan pretreatment can decrease cerebral infarct area induced by MCAO through improvement of focal cerebral blood flow after MCAO.