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Intravenously injected CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock: effect is mediated by central cholinergic activation.

Abstract：

:Intravenous (i.v.) administration of cytidine-5'-diphosphate choline (CDP-choline) (100, 250 and 500 mg/kg) increased blood pressure in normal rats and reversed hypotension in haemorrhagic shock. Choline (54 mg/kg; i.v.), at the dose equimolar to 250 mg/kg CDP-choline decreased blood pressure of rats in both conditions and caused the death of all hypotensive animals within 2-5 min. Equimolar dose of cytidine (124 mg/kg; i.v.) did not change cardiovascular parameters. Choline levels in plasma, lateral cerebral ventricle and hypothalamus increased after CDP-choline administration. Intracerebroventricular (i.c.v.) hemicholinium-3 pretreatment (20 microg), greatly attenuated the pressor effect of CDP-choline in both conditions. Atropine pretreatment (10 microg; i.c.v.) did not change the pressor effect of CDP-choline while mecamylamine (50 microg; i.c.v.) abolished the pressor response to drug. Besides, acetylcholine (1 micromol; i.c.v.) produced similar increases in blood pressure in normal and hypotensive conditions to that observed in CDP-choline given rats. CDP-choline (250 mg/kg; i.v.) increased plasma catecholamines and vasopressin levels but not plasma renin activity. Pretreatment of rats with either prazosin (0.5 mg/kg; i.v.) or vasopressin V(1) receptor antagonist, [beta-mercapto,beta,beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2)-Arg(8)]vasopressin (10 microg/kg; i.v.), attenuated the pressor response to CDP-choline while simultaneous administration of these antagonists before CDP-choline injection completely blocked the pressor effect. Results show that i.v. CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock. Activation of central nicotinic cholinergic mechanisms by the increases in plasma and brain choline concentrations appears to be involved in the pressor effect of this drug. Moreover, the increases in plasma catecholamines and vasopressin levels mediate these effects.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Savci V,Goktalay G,Cansev M,Cavun S,Yilmaz MS,Ulus IH

doi

10.1016/s0014-2999(03)01602-9

keywords:

subject

Has Abstract

pub_date

2003-05-09 00:00:00

pages

129-39

issue

eissn

0014-2999

issn

1879-0712

pii

S0014299903016029

journal_volume

468

pub_type

杂志文章

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Intravenously injected CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock: effect is mediated by central cholinergic activation.