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Involvement of the histaminergic system in cytidine 5'-diphosphocholine-induced reversal of critical haemorrhagic hypotension in rats

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Jochem J., Savci V., Filiz N., Rybus-Kalinowska B., Fogel W. A., Yalcin M.

Journal of Physiology and Pharmacology

2010

tom 61

nr 1

37-43

Cytidine 5’-diphosphocholine (CDP-choline) is an endogenously synthesized mononucleotide which exerts a variety of physiological effects by altering central cholinergic transmission. Administered intracerebroventricularly (i.c.v.) or intravenously, it reverses haemorrhagic hypotension in rats, apparently by the activation of central cholinergic receptors. The study was undertaken to investigate the involvement of the central histaminergic system in CDP-choline-mediated reversal of haemorrhagic hypotension. Experiments were carried out in male ketamine/xylazine-anaesthetised Wistar rats subjected to haemorrhagic hypotension of 20-26 mmHg. CDP-choline (2 µmol; i.c.v.) administered at 5 min of critical hypotension produced a long-lasting pressor effect with increases in mean arterial pressure (MAP), heart rate (HR), and renal, hindquarters and mesenteric blood flows, resulting in a 100% survival at 2 h. The action was accompanied by approximately a 26% increase in extracellular histamine concentration at the posterior hypothalamus, as measured by microdialysis. Cardiovascular effects mediated by CDP-choline were almost completely blocked by pretreatment with H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.), but not with H2 receptor blocker ranitidine (25 nmol; icv) or H3/H4 receptor antagonist thioperamide (50 nmol; i.c.v.). In conclusion, the present results show that the central histaminergic system, through the activation of H1 histaminergic receptors, is involved in CDP-choline-induced resuscitating effect in haemorrhage-shocked rats.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Filiz N.

1 Fogel W. A.

1 Jochem J.

1 Rybus-Kalinowska B.

1 Savci V.

1 Yalcin M.

1 2010

Wyniki wyszukiwania

Involvement of the histaminergic system in cytidine 5'-diphosphocholine-induced reversal of critical haemorrhagic hypotension in rats