Reversal of haemorrhagic shock in rats by cholinomimetic drugs

Abstract

1 In an experimental model of haemorrhagic shock resulting in the death of all rats within 20-30min, the intravenous (i.v.) injection of the tertiary amine cholinesterase inhibitor physostigmine (17-701pgkg-1) 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. 2 Similar results were obtained with the i.v. injection of the cholinoceptor agonist oxotremorine (5-25 pgkg-1), while neostigmine (54 or 70ygkg-), a quaternary cholinesterase inhibitor which cannot cross the blood-brain barrier, had negligible effects. 3 The anti-shock activities of oxotremorine and physostigmine were blocked by the intracerebroventricular injection of either of the combined nicotinic and M2-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 M1-and M2-muscarinic receptor antagonist atropine, the M1-muscarinic receptor antagonist pirenzepine, or the M2-muscarinic receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide. 4 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.

Restoration of blood pressure by choline treatment in rats made hypotensive by haemorrhage

“…choline in the haemorrhaged rats was mediated solely by central nicotinic receptors. It has recently been reported that intravenous administration of oxotremorine or physostigmine restores blood pressure and increases the survival rate in haemorrhaged rats (Guarini et al, 1989), an effect also mediated by central nicotinic receptors. The present results are in good accordance with this report.…”

“…Pharmacological activation of brain cholinergic neurotransmission results in an increase in blood pressure in several vertebrate species, including rat, dog and man (Brezenoff & Guiliano, 1982). More recently, it has been reported that the centrally acting drugs, oxotremorine and physostigmine, can restore blood pressure and increased survival rate of rats in an experimental haemorrhagic shock model (Guarini et al, 1989). Based on these observations it has been suggested that an increase in central cholinergic tone is involved in the development and maintenance of hypertension (Brezenoff, 1984), while a decrease in central cholinergic tone is involved in the complex pathophysiology of cardiovascular shock (Guarini et al, 1989).…”

“…It is likely that free choline supply to brain cholinergic neurones from the circulation also is diminished during haemorrhagic hypotension and shock, and a suggested decrease (Guarini et al, 1989) in brain cholinergic tone during haemorrhagic shock may result from the decrease in free choline supply. If so, providing extra free choline to central cholinergic neurones might restore central cholinergic neurotransmission and help to restore blood pressure.…”

Role of neuronal and vascular Ca2+‐channels in the ACTH‐induced reversal of haemorrhagic shock

“…not significantly different) in all experimental groups. As previously described (Bertolini et al, 1986a,b,c;1989;Guarini et al, 1989;1990b), the acute hypovolaemia induced in our model of volume-controlled haemorrhagic shock in anaethetized rats was incompatible with survival, all salinetreated animals dying within 26 ± 3 min after treatment. On the other hand, and again in agreement with previous results (Bertolini et al, 1986a,b,c;1989;Guarini et al, 1990a,b,c), the timely i.v.…”

Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine

“…acetylcholine itself, carbachol, oxotremorine or indirectly acting cholinergic agents, including the acetylcholine precursor choline and the acetylcholinesterase inhibitors physostigmine and neostigmine, increase blood pressure by activating central cholinergic mechanisms in conscious and anaesthetised animals [1,[3][4][5][6]. Recent studies reported that the centrally acting cholinergic drugs including choline, oxotremorine and physostigmine can restore blood pressure and increase the survival rate of rats under several hypotensive conditions such as experimental haemorrhagic shock [7][8][9], endotoxic shock [10], spinal shock [11] or even after prolonged respiratory arrest [12]. Observations from these experiments suggested that a decrease in central cholinergic tone is involved in the complex pathophysiology of shock.…”