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Reversal of haemorrhagic shock in rats by cholinomimetic drugs

British Journal of Pharmacology, ISSN: 0007-1188, Vol: 98, Issue: 1, Page: 218-224
1989
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In an experimental model of haemorrhagic shock resulting in the death of all rats within 20-30 min, the intravenous (i.v.) injection of the tertiary amine cholinesterase inhibitor physostigmine (17-70 μg kg) induced a prompt, sustained and dose-dependent improvement of cardiovascular and respiratory function, with marked increase in the volume of circulating blood and survival of all treated animals, at least for the 2 h of observation. Similar results were obtained with the i.v. injection of the cholinoceptor agonist oxotremorine (5-25 μg kg), while neostigmine (54 or 70 μg kg), a quaternary cholinesterase inhibitor which cannot cross the blood-brain barrier, had negligible effects. The anti-shock activities of oxotremorine and physostigmine were blocked by the intracerebroventricular injection of either of the combined nicotinic and M-muscarinic receptor antagonists gallamine and pancuronium, or of the nicotinic antagonist mecamylamine. They were also blocked by intraperitoneal injection of the adrenergic neurone blocking agent guanethidine, but they were not antagonized by either the combined M- and M-muscarinic receptor antagonist atropine, the M-muscarinic receptor antagonist pirenzepine, or the M-muscarinic receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide. It is concluded that cholinomimetic drugs can reverse hypovolaemic shock through central activation (seemingly mediated by nicotinic receptors) of sympathetic tone, with mobilization and redistribution of the residual blood.

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