Tracy H A, Wayner M J, Armstrong D L
Division of Life Sciences, University of Texas at San Antonio 78249-0662, USA.
Alcohol. 1996 May-Jun;13(3):287-9. doi: 10.1016/0741-8329(95)02057-8.
The purpose of the present study was to determine the effects of an angiotensin II (AII) AT1 antagonist, losartan 10, 15, and 20 mg/kg IP, and the AII AT2 antagonist, PD 123319, 20 mg/kg IP on ethanol (EtOH) intoxication as measured by the aerial righting reflex in male rats. EtOH (25%), 2.0 g/kg, was administered by stomach tube under mild metaphane anesthesia and the aerial righting reflex was determined at 30-min intervals for 3.5 h. The AII antagonists were administered IP 2 h before the EtOH. There were six groups of 10 rats each: EtOH alone, 10, 15, or 20 mg/kg losartan plus ethanol, 20 mg/kg losartan plus 20 mg/kg PD 123319 plus EtOH, and 20 mg/kg losartan alone. Data were analyzed by a two-way ANOVA with repeated measures on one factor, time. Results show a clear intoxicating effect of ethanol on the aerial righting reflex that was blocked significantly by losartan in a dose-dependent way. Losartan alone had no observable effect. The administration of both antagonists, losartan and PD 123319 injected IP in two different sites, completely blocked the EtOH effect on the aerial righting reflex. The involvement of AII in the mediation of EtOH intoxication effects on the aerial righting reflex supports results of our previous studies on the effects of EtOH on open field behavior, AII impairment of the retention of an inhibitory shock avoidance response, and AII inhibition of hippocampal granule cell long-term potentiation, all of which can be blocked by losartan.
本研究的目的是确定血管紧张素II（AII）AT1拮抗剂（腹腔注射10、15和20mg/kg氯沙坦）以及AII AT2拮抗剂（腹腔注射20mg/kg PD 123319）对雄性大鼠乙醇（EtOH）中毒的影响，中毒程度通过空中翻正反射来衡量。在轻度甲氟烷麻醉下，通过胃管给予2.0g/kg的EtOH（25%），并在3.5小时内每隔30分钟测定一次空中翻正反射。AII拮抗剂在给予EtOH前2小时腹腔注射。共有六组，每组10只大鼠：单独给予EtOH、10、15或20mg/kg氯沙坦加乙醇、20mg/kg氯沙坦加20mg/kg PD 123319加乙醇以及单独给予20mg/kg氯沙坦。数据采用单因素重复测量的双向方差分析进行分析，因素为时间。结果显示，乙醇对空中翻正反射有明显的中毒作用，氯沙坦能以剂量依赖的方式显著阻断该作用。单独使用氯沙坦没有可观察到的效果。同时给予两种拮抗剂，即分别在两个不同部位腹腔注射氯沙坦和PD 123319，能完全阻断EtOH对空中翻正反射的作用。AII参与介导EtOH对空中翻正反射的中毒作用，这支持了我们之前关于EtOH对旷场行为的影响、AII对抑制性回避电击反应记忆的损害以及AII对海马颗粒细胞长时程增强的抑制作用的研究结果，所有这些作用都能被氯沙坦阻断。
