Cardiovascular effects of histamine H3 receptor antagonist JNJ 5207852 in haemorrhagic shock in rats
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Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia
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Jerzy Jochem   

Katedra i Zakład Podstawowych Nauk Medycznych Wydziału Zdrowia Publicznego w Bytomiu Śląskiego Uniwersytetu Medycznego w Katowicach, ul. Piekarska 18, 41-902 Bytom, tel. +48 32 397 65 45
Ann. Acad. Med. Siles. 2016;70:89-94
Histamine H3 receptors are widely distributed in the central and peripheral nervous system, including postganglionic adrenergic endings. They act mainly as presynaptic auto- and heteroceptors and are responsible for regulating the synthesis and release of histamine and other neurotransmitters/neuromodulators. The aim of the study was to examine the cardiovascular effects of the histamine H3 receptor blockade in the sympathoinhibitory phase of haemorrhagic shock.

Material and methodss:
Studies were carried out on male Wistar rats anaesthetized with ketamine/xylazine (100 mg/kg + 10 mg/kg, intraperitoneally), subjected to irreversible haemorrhagic shock (0% survival at 2 h) with a mean arterial pressure (MAP) of 20–25 mmHg. At 5 min of critical hypotension, the rats were injected intravenously with H3 receptor antagonist JNJ 5207852 or saline.

Haemorrhage led to a decrease in pulse pressure (PP) and heart rate (HR). JNJ 5207852 (1 and 5 mg/kg) evoked long-lasting rises in MAP, PP and HR, with an improvement in survival at 2 h (5 mg/kg). Chemical sympathectomy with 6-hydroxydopamine (50 mg/kg for three consecutive days) inhibited cardiovascular changes evoked by JNJ 5207852 and decreased to 0% the survival rate at 2 h in rats treated with JNJ 5207852 (5 mg/kg).

Histamine H3 receptor antagonist JNJ 5207852 induces the resuscitating effect in haemorrhage-shocked rats, and the mechanism responsible is associated with the activity of postganglionic sympathetic neurons.

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Markus Falkenstein, Milica Elek, Holger Stark
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