DOPAMINE D-1 RECEPTORS ARE INVOLVED IN THE ACTH-INDUCED REVERSAL OF HEMORRHAGIC-SHOCK

In an experimental model of volume-controlled hemorrhagic shock causin g the death of all rats within 30 min, the intravenous (i.v.) bolus in jection of the adrenocorticotropic hormone fragment 1-24 (ACTH-(1-24)) (160 mu g/kg) induced a prompt and sustained improvement of cardiovas cular and respiratory function, with 100% survival 2 h after treatment . Pretreatment with either haloperidol, 300 mu g/kg i.v. (antagonist a t dopamine D-1 and D-2 receptors), or -tetrahydro-3-methyl-5-phenyl-1H -3-benzazepin-7-ol hemimaleate (SCH 23390), 50 mu g/kg intraperitoneal ly (selective antagonist at dopamine D-1 receptors), significantly inh ibited the effect of ACTH-(1-24). A complete inhibition was produced b y intracerebroventricular pretreatment with SCH 23390 (0.1 mu g/rat). On the other hand, both i.v. and i.c.v. pretreatment with l-sulpiride (selective antagonist at dopamine D-2 receptors) (25 mg/kg and 80 mu g /rat, respectively) had only minor effects. These data suggest that th e mechanism of the ACTH-induced reversal of hemorrhagic shock involves the activation of dopamine D-1 receptors in the brain.