Bazzani C, Nardi M G, Ferrante F, Bertolini A, Guarini S
Institute of Pharmacology, University of Modena, Italy.
Eur J Pharmacol. 1994 Mar 3;253(3):303-6. doi: 10.1016/0014-2999(94)90207-0.
In an experimental model of volume-controlled hemorrhagic shock causing the death of all rats within 30 min, the intravenous (i.v.) bolus injection of the adrenocorticotropic hormone fragment 1-24 (ACTH-(1-24)) (160 micrograms/kg) induced a prompt and sustained improvement of cardiovascular and respiratory function, with 100% survival 2 h after treatment. Pretreatment with either haloperidol, 300 micrograms/kg i.v. (antagonist at dopamine D1 and D2 receptors), or (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol hemimaleate (SCH 23390), 50 micrograms/kg intraperitoneally (selective antagonist at dopamine D1 receptors), significantly inhibited the effect of ACTH-(1-24). A complete inhibition was produced by intracerebroventricular pretreatment with SCH 23390 (0.1 micrograms/rat). On the other hand, both i.v. and i.c.v. pretreatment with l-sulpiride (selective antagonist at dopamine D2 receptors) (25 mg/kg and 80 micrograms/rat, respectively) had only minor effects. These data suggest that the mechanism of the ACTH-induced reversal of hemorrhagic shock involves the activation of dopamine D1 receptors in the brain.
在容量控制型失血性休克实验模型中，该模型可导致所有大鼠在30分钟内死亡，静脉推注促肾上腺皮质激素片段1 - 24（ACTH - (1 - 24)）（160微克/千克）可迅速并持续改善心血管和呼吸功能，治疗后2小时存活率达100%。分别用氟哌啶醇（300微克/千克，静脉注射，多巴胺D1和D2受体拮抗剂）或（R）-（+）-8 - 氯 - 2,3,4,5 - 四氢 - 3 - 甲基 - 5 - 苯基 - 1H - 3 - 苯并氮杂卓 - 7 - 醇半马来酸盐（SCH 23390，50微克/千克，腹腔注射，多巴胺D1受体选择性拮抗剂）进行预处理，可显著抑制ACTH - (1 - 24)的作用。脑室内用SCH 23390（0.1微克/只大鼠）预处理可产生完全抑制作用。另一方面，静脉和脑室内用l - 舒必利（多巴胺D2受体选择性拮抗剂）（分别为25毫克/千克和80微克/只大鼠）预处理仅有轻微作用。这些数据表明，ACTH诱导失血性休克逆转的机制涉及脑内多巴胺D1受体的激活。
