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

Summary 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 g/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. Send offprint requests to S. Guarini at the above address