Effects of nitric oxide-related agents on alcohol narcosis.
Effects of nitric oxide-related agents on alcohol narcosis.
复制标题
一氧化氮相关药物对酒精麻醉的影响。
DOI：
10.1111/j.1530-0277.1994.tb00068.x
复制
发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Cicero,TJ
中科院分区：
文献类型：
--
作者：
Adams,ML;Meyer,ER;Sewing,BN;Cicero,TJ
为了检查一氧化氮 (NO) 是否影响酒精（乙醇）麻醉，成年雄性大鼠用一氧化氮合酶 (NOS) 抑制剂 NG-硝基-i-精氨酸甲酯 (NAME) 进行预处理； NOS 底物 I-精氨酸甲酯 (AME)；或NO供体，硝酸异山梨酯(ISDN)；然后用麻醉剂量（3-5 g/kg，腹腔注射）的酒精进行治疗。在酒精治疗前 40 分钟用 NAME（30-100 mg/kg，皮下注射）进行预处理，可延迟酒精引起的翻正反射丧失 (LORR) 的发生，并延长 LORR 的持续时间。 NAME（100 mg/kg）预处理与高剂量酒精（4-5 g/kg）相结合产生了显着的致死作用，尽管单独使用任一药物或NAME与较低剂量酒精（3-3.5 g/kg）相结合的治疗并不致命。同时使用 NOS 底物 AME（100 mg/kg，皮下）治疗可阻断 NAME 对 LORR 持续时间的影响，但不会改变 LORR 起始时间。在饮酒前 2 小时通过口服强饲法给予 NO 供体 ISDN (30 mg/kg)，可缩短 LORR 持续时间，但不影响 LORR 的发作。此外，ISDN 剂量依赖性地抑制酒精麻醉期间 NAME 诱导的 LORR 持续时间增加，但不会显着改变 LORR 的起始时间。 ISDN 和 NAME 均未显着改变血液中的酒精浓度。这些结果表明，NOS 抑制和随后 NO 产生的减少增强了酒精诱导的麻醉，而 NO 浓度的增加抑制了酒精麻醉，支持了精氨酸-NOS-NO 系统的抑制介导酒精部分镇静催眠作用的假设。
To examine whether nitric oxide (NO) affects alcohol (ethanol) narcosis, adult male rats were pretreated with a NO synthase (NOS) inhibitor, NG‐nitro‐i‐arginine methyl ester (NAME); a NOS substrate, I‐arginine methyl ester (AME); or a NO donor, isosorbide dinitrate (ISDN); then treated with anesthetic doses (3–5 g/kg, ip) of alcohol. Pretreatment with NAME (30–100 mg/kg, sc) 40 min before alcohol treatment delayed the onset of alcohol‐induced loss of the righting reflex (LORR) and increased the duration of the LORR. NAME (100 mg/kg) pretreatment combined with high doses of alcohol (4–5 g/kg) exerted significant lethal effects, even though treatment with either agent alone or NAME combined with lower doses of alcohol (3–3.5 g/kg) was not lethal. Simultaneous treatment with the NOS substrate AME (100 mg/kg, subcutaneous) blocked the effects of NAME on LORR duration times, but did not alter LORR onset times. The NO donor ISDN (30 mg/kg) given by oral gavage 2 hr before alcohol decreased LORR duration times without affecting the onset of LORR. In addition, ISDN dose‐dependently inhibited NAME‐induced LORR duration increases during alcohol narcosis without significantly altering LORR onset times. Neither ISDN nor NAME significantly altered blood alcohol concentrations. These results suggest that NOS inhibition and subsequent decreases in NO production enhance alcohol‐induced narcosis and that increases in NO concentrations inhibit alcohol narcosis, supporting the hypothesis that inhibition of arginine‐NOS‐NO systems mediates part of the sedative‐hypnotic effect of alcohol.