ANGIOTENSIN-II ANTAGONISTS BLOCK ETHANOL EFFECTS ON THE AERIAL RIGHTING REFLEX

The purpose of the present study was to determine the effects of an an giotensin II (AII) AT(1) antagonist, losartan 10, 15, and 20 mg/kg IP, and the AII AT(2) 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 met aphane 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 analyze d by a two-way ANOVA with repeated measures on one factor, time. Resul ts 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 bo th antagonists, losartan and PD 123319 injected IP in two different si tes, 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 inhibitio n of hippocampal granule cell long-term potentiation, all of which can be blocked by losartan.