Brain M3 muscarinic receptors are involved in the ACTH-induced reversal of hemorrhagic shock.

In an experimental model of bleeding-induced hemorrhagic shock causing the death of all saline-treated rats within 30 min, the intravenous injection of ACTH-(1-24) at the dose of 160 micrograms/kg induced a sustained reversal of the shock condition, with almost complete recovery of blood pressure, pulse amplitude, respiratory rate, heart rate, and 100% survival, at least for the 2 h of observation. This effect of ACTH-(1-24) was prevented by the intracerebroventricular injection of 4-DAMP (a highly selective antagonist for M1 and M3 muscarinic receptors), but unaffected by the intracerebroventricular injection of pirenzepine (a highly selective antagonist for M1 muscarinic receptors). These data indicate that an essential step in the complex mechanism of the ACTH-induced shock reversal may be the activation of brain M3 muscarinic receptors.