Adrenocorticotropic hormone (ACTH) and centrally-acting cholinomimetic drugs improve survival of rats with severe hemorrhagic shock through distinct central cholinergic mechanisms.
Pharmacological doses (40-160 micrograms/kg) of adrenocorticotropic hormone (ACTH) intravenously injected to urethane-anesthetized rats subjected to otherwise lethal hemorrhagic shock (mean arterial pressure stabilized at 20-25 mmHg) promptly restore blood pressure to about the pre-bleeding values, and prevent death (anti-shock effect). Hemicholinium-3 (i.c.v. injected) and atropine sulphate, but not atropine methylbromide, antagonize these ACTH effects. Moreover, since pirenzepine, injected i.v. or i.c.v., does not affect the anti-shock activity of ACTH, the central cholinergic mechanism participating in this ACTH action must involve M2, but not M1 brain muscarinic receptors. Intravenous physostigmine, too (but not neostigmine) and oxotremorine have an ACTH-like anti-shock effect, which however is neither affected by hemicholinium-3, nor by atropine methylbromide, nor by atropine sulphate, but only by high i.c.v. doses of gallamine or pancuronium. On the other hand, reserpine, guanethidine, and alpha-adrenoceptor blocking drugs inhibit the anti-shock effect of ACTH as well as that of oxotremorine and physostigmine. It is suggested that, in rats, both ACTH and cholinergic drugs must activate a central cholinergic mechanism(s) in order to exert a sympathetic nerve-mediated anti-shock effect. However, receptors involved are of the muscarinic M2 subtype in the case of ACTH, and probably nicotinic in the case of cholinergic drugs. That ACTH and cholinergic drugs activate different central cholinergic mechanisms is also suggested by the fact that cholinergic drugs have a centrally-mediated hypertensive action in normal animals, which is not shared by ACTH.
Bertolini
A
A
Institute of Pharmacology, University of Modena, Italy.
Ferrari
W
W
Guarini
S
S
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D006426:Hemicholinium 3 / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D012018:Reflex; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology
D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D006426:Hemicholinium 3; D000324:Adrenocorticotropic Hormone