Jochem, JerzyRybus-Kalinowska, BarbaraFogel, Wiesława Agnieszka2022-01-142022-01-142010-02Jochem, J. vd. (2010). "Involvement of the histaminergic system in cytidine 5'-diphosphocholine-induced reversal of critical haemorrhagic hypotension in rats". Journal of Physiology and Pharmacology, 61(1), 37-43.0867-5910http://hdl.handle.net/11452/24095Cytidine 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 mu mol; 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 H(1) receptor antagonist chlorpheniramine (50 nmol; i.c.v.), but not with H(2) receptor blocker ranitidine (25 nmol; icv) or H(3)/H(4) receptor antagonist thioperamide (50 nmol; i.c.v.). In conclusion, the present results show that the central histaminergic system, through the activation of H(1) histaminergic receptors, is involved in CDP-choline-induced resuscitating effect in haemorrhage-shocked rats.eninfo:eu-repo/semantics/openAccessHaemorrhagic shockHistamineCytosine 5 '-diphosphocholineMicrodialysisMean arterial pressureHeart rateEndogenous central histamineInjected CDP-cholineBlood-pressureCardiovascular-responsesIncreasesReleaseStressBrainProstaglandisShockPhysiologyAnimalsCytidine diphosphate cholineHistamineHistamine H1 antagonistsHypotensionMaleRatsRats, wistarReceptors, histamine H1Shock, hemorrhagicArticle0002753923000062-s2.0-77954303379374361120228413PhysiologyHistamine H4 Receptors; Thioperamide; Chlorpheniramine MaleateChlorpheniramineCiticolineHistamineRanitidineThioperamideCiticolineHistamineHistamine H1 receptorHistamine H1 receptor antagonistAnimal experimentAnimal modelArticleCholinergic systemControlled studyDrug efficacyDrug mechanismExtracellular spaceHeart rateHemorrhagic hypotensionKidney blood flowMaleMean arterial pressureMesentery blood flowNonhumanPressor responseRatSurvival rateSurvival timeAnimalComparative studyHypotensionPathophysiologyPhysiologyShock, hemorrhagicWistar rat